[1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds

ABSTRACT

or a salt thereof, wherein R1, R2, R3, R4, R5, m, n, and p are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 15/635,055 filed Jun. 27, 2017, which claims thebenefit of Indian Provisional Application Serial No. 201611022328, filedJun. 29, 2016, which is incorporated herein in its entirety.

The present invention generally relates to[1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds useful asinhibitors of signaling through Toll-like receptor 7, 8, or 9 (TLR7,TLR8, TLR9) or combinations thereof. Provided herein are[1,2,4]triazolo[1,5-a] pyridinyl substituted indole compounds,compositions comprising such compounds, and methods of their use. Theinvention further pertains to pharmaceutical compositions containing atleast one compound according to the invention that are useful for thetreatment of conditions related to TLR modulation, such as inflammatoryand autoimmune diseases, and methods of inhibiting the activity of TLRsin a mammal.

Toll/IL-1 receptor family members are important regulators ofinflammation and host resistance. The Toll-like receptor familyrecognizes molecular patterns derived from infectious organismsincluding bacteria, fungi, parasites, and viruses (reviewed in Kawai, T.et al., Nature Immunol., 11:373-384 (2010)). Ligand binding to thereceptor induces dimerization and recruitment of adaptor molecules to aconserved cytoplasmic motif in the receptor termed the Toll/IL-1receptor (TIR) domain. With the exception of TLR3, all TLRs recruit theadaptor molecule MyD88. The IL-1 receptor family also contains acytoplasmic TIR motif and recruits MyD88 upon ligand binding (reviewedin Sims, J. E. et al., Nature Rev. Immunol., 10:89-102 (2010)).

Toll-like receptors (TLRs) are a family of evolutionarily conserved,transmembrane innate immune receptors that participate in the first-linedefense. As pattern recognition receptors, the TLRs protect againstforeign molecules, activated by pathogen associated molecular patterns(PAMPs), or from damaged tissue, activated by danger associatedmolecular patterns (DAMPs). A total of 13 TLR family members have beenidentified, 10 in human, that span either the cell surface or theendosomal compartment. TLR7-9 are among the set that are endosomallylocated and respond to single-stranded RNA (TLR7 and TLR8) orunmethylated single-stranded DNA containing cytosine-phosphate-guanine(CpG) motifs (TLR9).

Activation of TLR7/8/9 can initiate a variety of inflammatory responses(cytokine production, B cell activation and IgG production, Type Iinterferon response). In the case of autoimmune disorders, the aberrantsustained activation of TLR7/8/9 leads to worsening of disease states.Whereas overexpression of TLR7 in mice has been shown to exacerbateautoimmune disease, knockout of TLR7 in mice was found to be protectiveagainst disease in lupus-prone MRL/lpr mice. Dual knockout of TLR7 and 9showed further enhanced protection.

As numerous conditions may benefit by treatment involving modulation ofcytokines, IFN production and B cell activity, it is immediatelyapparent that new compounds capable of modulating TLR7 and/or TLR8and/or TLR9 and methods of using these compounds could providesubstantial therapeutic benefits to a wide variety of patients.

The present invention relates to a new class of[1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds found to beeffective inhibitors of signaling through TLR7/8/9. These compounds areprovided to be useful as pharmaceuticals with desirable stability,bioavailability, therapeutic index, and toxicity values that areimportant to their drugability.

SUMMARY OF THE INVENTION

The present invention provides compounds of Formula (I) that are usefulas inhibitors of signaling through Toll-like receptor 7, 8, or 9 and areuseful for the treatment of proliferative diseases, allergic diseases,autoimmune diseases and inflammatory diseases, or stereoisomers,tautomers, pharmaceutically acceptable salts, solvates or prodrugsthereof.

The present invention also provides pharmaceutical compositionscomprising a pharmaceutically acceptable carrier and at least one of thecompounds of the present invention or stereoisomers, tautomers,pharmaceutically acceptable salts, solvates, or prodrugs thereof.

The present invention also provides a method for inhibition of Toll-likereceptor 7, 8, or 9 comprising administering to a host in need of suchtreatment a therapeutically effective amount of at least one of thecompounds of the present invention or stereoisomers, tautomers,pharmaceutically acceptable salts, solvates, or prodrugs thereof.

The present invention also provides a method for treating proliferative,metabolic, allergic, autoimmune and inflammatory diseases, comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of at least one of the compounds of the presentinvention or stereoisomers, tautomers, pharmaceutically acceptablesalts, solvates, or prodrugs thereof.

The present invention also provides a method of treating a disease ordisorder associated with Toll-like receptor 7, 8, or 9 activity, themethod comprising administering to a mammal in need thereof, at leastone of the compounds of Formula (I) or salts, solvates, and prodrugsthereof.

The present invention also provides processes and intermediates formaking the compounds of Formula (I) including salts, solvates, andprodrugs thereof.

The present invention also provides at least one of the compounds ofFormula (I) or salts, solvates, and prodrugs thereof, for use intherapy.

The present invention also provides the use of at least one of thecompounds of Formula (I) or salts, solvates, and prodrugs thereof, forthe manufacture of a medicament for the treatment of prophylaxis ofToll-like receptor 7, 8, or 9 related conditions, such as allergicdisease, autoimmune diseases, inflammatory diseases, and proliferativediseases.

The compound of Formula (I) and compositions comprising the compounds ofFormula (I) may be used in treating, preventing, or curing variousToll-like receptor 7, 8, or 9 related conditions. Pharmaceuticalcompositions comprising these compounds are useful for treating,preventing, or slowing the progression of diseases or disorders in avariety of therapeutic areas, such as allergic disease, autoimmunediseases, inflammatory diseases, and proliferative diseases.

These and other features of the invention will be set forth in expandedform as the disclosure continues.

DETAILED DESCRIPTION

The first aspect of the present invention provides at least one compoundof Formula (I):

or a salt thereof, wherein:

-   R₁ is H, Cl, —CN, C₁₋₄ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃    hydroxy-fluoroalkyl, —CR_(z)═CH₂, C₃₋₆ cycloalkyl, —CH₂(C₃₋₆    cycloalkyl), —C(O)O(C₁₋₃ alkyl), or tetrahydropyranyl;-   each R₂ is independently halo, —CN, —OH, —NO₂, C₁₋₃ alkyl, —CD₃,    C₁₋₂ fluoroalkyl, C₁₋₂ cyanoalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃    aminoalkyl, —O(CH₂)₁₋₂OH, —(CH₂)₀₋₄O(C₁₋₄ alkyl), C₁₋₃ fluoroalkoxy,    —(CH₂)₁₋₄O(C₁₋₃ alkyl), —O(CH₂)₁₋₂OC(O)(C₁₋₃ alkyl),    —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃ alkyl), —C(O)NR_(y)R_(y),    —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄ hydroxyalkyl),    —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), —NR_(x)C(O)(C₁₋₃    alkyl), —NR_(x)(CH₂-cyclopropyl), C₃₋₆ cycloalkyl, morpholinyl,    dioxothiomorpholinyl, methylpiperidinyl, methylpiperazinyl,    amino-oxadiazolyl, imidazolyl, triazolyl, or —C(O)(thiazolyl);-   R₃ is:    -   (a) -L₁-A; or    -   (b) H, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ cyanoalkyl, C₁₋₆        hydroxyalkyl, C₁₋₃ hydroxy-fluoroalkyl,        —CR_(x)R_(x)CR_(x)(OH)CR_(x)═CR_(x)R_(x), —C═N(NR_(x)R_(x)),        —(CR_(x)R_(x))₁₋₄O(C₁₋₃ alkyl),        —(CR_(x)R_(x))₁₋₄O(CR_(x)R_(x))₁₋₃O(C₁₋₃ alkyl),        —CH₂CH(OH)CH₂O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),        —(CH₂)₁₋₃C(O)OC(CH₃)₃, —(CR_(x)R_(x))₀₋₃NR_(x)R_(y),        —(CR_(x)R_(x))₀₋₃NR_(x)(C₁₋₄ hydroxyalkyl),        —CH₂CH(OH)CH₂NR_(x)R_(y), —C(O)H, —C(O)(C₁₋₆ alkyl), —C(O)(C₁₋₄        hydroxyalkyl), —C(O)(C₁₋₃ fluoroalkyl), —C(O)(C₁₋₃ chloroalkyl),        —C(O)(C₁₋₃ cyanoalkyl), —(CR_(x)R_(x))₀₋₃C(O)OH,        —C(O)(CH₂)₀₋₂O(C₁₋₄ alkyl),        —C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂O(C₁₋₃ alkyl),        —C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂NR_(y)R_(y),        —C(O)CR_(x)R_(x)S(O)₂(C₁₋₃ alkyl),        —C(O)CR_(x)R_(x)NR_(x)S(O)₂(C₁₋₃ alkyl),        —C(O)CR_(x)R_(x)OC(O)(C₁₋₃ alkyl),        —C(O)(CR_(x)R_(x))₀₋₃NR_(y)R_(y),        —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₃ cyanoalkyl),        —C(O)(CR_(x)R_(x))₀₋₂NR_(y)(C₁₋₆ hydroxyalkyl),        —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(C₁₋₃ fluoroalkyl),        —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₅ hydroxy-fluoroalkyl),        —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂O(C₁₋₃ hydroxyalkyl),        —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₂ alkyl),        —C(O)(CR_(x)R_(x))₀₋₂NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),        —C(O)(CR_(x)R_(x))₀₋₂N((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl))₂,        —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₁₋₃NR_(x)R_(x),        —C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)R_(x),        —C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)C(O)NR_(x)R_(x),        —C(O)(CR_(x)R_(x))₀₋₃NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ alkyl),        —C(O)(CR_(x)R_(x))₀₋₃N((CH₂)₀₋₁C(O)(C₁₋₃ alkyl))₂,        —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ cyanoalkyl),        —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),        —C(O)(CR_(x)R_(x))₁₋₃C(O)NR_(y)R_(y),        —C(O)(CR_(x)R_(x))₁₋₃S(O)₂NR_(y)R_(y),        —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CHR_(y)(CH₂OH)),        —(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y), —CH(CN)C(O)NR_(y)R_(y),        —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃ fluoroalkyl),        —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₄ hydroxyalkyl),        —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃ cyanoalkyl),        —(CR_(x)R_(x))₁₋₂C(O)NR_(x)(CH₂)₁₋₂O(C₁₋₃ alkyl),        —(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₄ alkyl)(C₁₋₃ hydroxyalkyl),        —(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₃ hydroxyalkyl)(C₃₋₆        cycloalkyl), —(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂C(O)NR_(x)R_(x),        —(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(C₁₋₃ alkyl),        —(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(O)₂OH,        —(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₃ alkyl),        —(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₃NR_(x)R_(x),        —(CH₂)₁₋₂C(O)N(CH₂CH₃)(CH₂)₁₋₃NR_(x)R_(x), —(CR_(x)R_(x))₀₋₃        S(O)₂(C₁₋₄ alkyl), —(CH₂)₀₋₂S(O)₂(C₁₋₃ fluoroalkyl),        —(CR_(x)R_(x))₀₋₂S(O)₂NR_(y)R_(y),        —(CR_(x)R_(x))₀₋₂NR_(x)S(O)₂(C₁₋₃ alkyl), —C(O)C(O)OH,        —C(O)C(O)NR_(y)R_(y), or        —C(O)C(O)NR_(y)(CR_(x)R_(x))₁₋₂NR_(y)R_(y);-   L₁ is a bond, —(CR_(x)R_(x))₁₋₂—, —(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,    —(CR_(x)R_(x))₁₋₂O—, —CR_(x)R_(x)C(O)—,    —(CR_(x)R_(x))₂NR_(x)(CR_(x)R_(x))₀₋₁—,    —CR_(x)R_(x)C(O)NR_(x)(CR_(x)R_(x))₀₋₄—, —C(O)(CR_(x)R_(x))₀₋₃—,    —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₀₋₂—,    —C(O)(CR_(x)R_(x))₀₋₂N(C₁₋₂ hydroxyalkyl)(CR_(x)R_(x))₀₋₂—,    —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,    —C(O)(CR_(x)R_(x))₁₋₂C(O)NR_(x),    —(CR_(x)R_(x))₀₋₂C(O)NR_(x)(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,    —(CR_(x)R_(x))₀₋₂C(O)N(C₁₋₂ hydroxyalkyl)(CR_(x)R_(x))₁₋₂—,    —C(O)(CR_(x)R_(x))₀₋₁O—, —C(O)(CR_(x)R_(x))₁₋₂NHS(O)₂—,    —C(O)CR_(x)(NH₂)CR_(x)R_(x), —C(O)C(O)(CR_(x)R_(x))₀₋₂—,    —C(O)NR_(x)(CR_(x)R_(x))₁₋₂—, or —S(O)₂—; A is    2-oxa-6-azaspiro[3,3]heptanyl, 4-oxaspiro[2.5]octanyl,    7-azaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl,    8-oxa-3-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl,    adamantanyl, azepanyl, azetidinyl, C₃₋₆ cycloalkyl, diazepanyl,    dihydroinonyl, dihydropyrimidinonyl, dioxanyl,    dioxidothiadiazinanyl, dioxidothiazolidinyl, dioxidothiomorpholinyl,    dioxoisothiazolidinyl, dioxidothiazinanyl,    dioxotetrahydrothiophenyl, dioxotetrahydrothiopyranyl,    dioxothiomorpholinyl, furanyl, imidazolyl, imidazolidinonyl,    indolyl, isoquinolinyl, isoxazolyl, morpholinyl, morpholinonyl,    naphthalenyl, octahydrocyclopenta[b]pyranyl,    octahydropyrrolo[3,4-b]pyridinyl, oxazolidinonyl, oxadiazolyl,    oxazolyl, oxetanyl, phenyl, piperidinyl, piperidinonyl, piperazinyl,    piperazinonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridazinonyl,    pyridinonyl, pyridinyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl,    pyrrolyl, quinolinyl, quinolizinonyl, tetrahydrofuranyl,    tetrahydropyranyl, tetrahydrothiopyranyl, tetrazolyl, thiadiazolyl,    thiazolyl, triazolonyl, or triazolyl, each substituted with    -L₂-R_(a) and zero to 4 R_(b);    L₂ is a bond or —CR_(x)R_(x)—;

R_(a) is:

(a) H, F, Cl, —CN, —OH, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₅ hydroxyalkyl,—(CH₂)₀₋₄O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₃NR_(y)R_(y),—(CR_(x)R_(x))₁₋₃C(O)NR_(y)R_(y), —O(C₁₋₃ fluoroalkyl),—S(O)₂NR_(x)R_(x), —O(CR_(x)R_(x))₁₋₃NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl),—NR_(x)R_(x), —NR_(x)(C₁₋₄ alkyl), —NR_(x)C(O)(C₁₋₄ alkyl),—(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(C₁₋₅ alkyl), —C(O)(C₁₋₃ fluoroalkyl),—C(O)O(C₁₋₄ alkyl), —C(O)NH(C₁₋₃ cyanoalkyl), —C(O)NR_(y)R_(y),—C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃ alkyl);(b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein each cycloalkylis substituted with zero to 2 substituents independently selected from—OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkyl, and —C(O)O(C₁₋₃alkyl); or(c) A₁, —CH₂A₁, —C(O)A₁, —NR_(x)A₁, or —C(O)NR_(x)A₁, wherein A₁ isfuranyl, imidazolyl, indolyl, isoxazolyl, morpholinyl,octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl,piperazinyl, piperidinyl, pyrazolyl, pyridinyl, pyrimidinyl,pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl,thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted withzero to three substituents independently selected from —OH, C₁₋₃ alkyl,C₁₋₃ hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃ alkyl), —NR_(x)R_(x),phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl), and—CH₂CH₂(pyrrolidinyl); each R_(b) is independently F, —OH, —CH₃, —CF₃,or —OCH₃;each R_(x) is independently H or —CH₃;each R_(y) is independently H or C₁₋₆ alkyl;R_(z) is H, C₁₋₂ alkyl, or C₁₋₂ fluoroalkyl;each R₄ is independently F, —OH, C₁₋₂ alkyl, or —OCH₃; or two R₄attached to the same carbon atom form ═O; or wherein when m is at least2, two R₄, each attached to a different carbon atom adjacent to thenitrogen atom in the piperidinyl ring, can form a —CH₂CH₂— bridge;each R₅ is independently F, Cl, —CN, C₁₋₂ alkyl, C₁₋₂ fluoroalkyl, or—OCH₃;m is zero, 1, 2, 3, or 4;n is zero, 1, or 2; andp is zero, 1, 2, 3, or 4.

The second aspect of the present invention provides at least onecompound of Formula (I) or a salt thereof, wherein:

R₁ is H, Cl, —CN, C₁₋₄ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃hydroxy-fluoroalkyl, —CR_(z)═CH₂, C₃₋₆ cycloalkyl, —CH₂(C₃₋₆cycloalkyl), —C(O)O(C₁₋₃ alkyl), or tetrahydropyranyl;each R₂ is independently halo, —CN, —OH, —NO₂ ⁺, C₁₋₃ alkyl, C₁₋₂fluoroalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl, —(CH₂)₀₋₄O(C₁₋₃ alkyl),C₁₋₃ fluoroalkoxy, C₂₋₄ alkoxyalkoxy, —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃alkyl), —C(O)NR_(y)R_(y), —NR_(y)R_(y), —NR_(x)C(O)(C₁₋₃ alkyl),—NR_(x)(CH₂-cyclopropyl), C₃₋₆ cycloalkyl, methylpiperidinyl,methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl, or—C(O)(thiazolyl);

R₃ is: (a) -L₁-A; or

(b) H, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ cyanoalkyl, C₁₋₆ hydroxyalkyl,C₁₋₃ hydroxy-fluoroalkyl, —CR_(x)R_(x)CR_(x)(OH)CR_(x)═CR_(x)R_(x),—(CR_(x)R_(x))₁₋₄O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₄O(CR_(x)R_(x))₁₋₃O(C₁₋₃alkyl), —CH₂CH(OH)CH₂O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),—(CH₂)₁₋₃C(O)OC(CH₃)₃, —(CR_(x)R_(x))₀₋₃NR_(x)R_(y),—(CR_(x)R_(x))₀₋₃NR_(x)(C₁₋₄ hydroxyalkyl), —CH₂CH(OH)CH₂NR_(x)R_(y),—C(O)H, —C(O)(C₁₋₆ alkyl), —C(O)(C₁₋₃ hydroxyalkyl), —C(O)(C₁₋₃fluoroalkyl), —C(O)(C₁₋₃ chloroalkyl), —C(O)(C₁₋₃ cyanoalkyl),—(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(CH₂)₀₋₂O(C₁₋₄ alkyl),—C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂O(C₁₋₃ alkyl),—C(O)CR_(x)R_(x)S(O)₂(C₁₋₃ alkyl), —C(O)CR_(x)R_(x)NR_(x)S(O)₂(C₁₋₃alkyl), —C(O)CR_(x)R_(x)OC(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₃NR_(y)R_(y), —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₃cyanoalkyl), —C(O)(CR_(x)R_(x))₀₋₂NR_(y)(C₁₋₆ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₃ fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₅ hydroxy-fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂O(C₁₋₃ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₂ alkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)C(O)N_(x)C(O)NR_(x)R_(x),—C(O)(CR_(x)R_(x))₀₋₃NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),—C(O)(CR_(x)R_(x))₁₋₃C(O)NR_(y)R_(y),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CHR_(y)(CH₂OH)),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃fluoroalkyl), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₄ hydroxyalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃ cyanoalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(CH₂)₁₋₂O(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₄ alkyl)(C₁₋₃ hydroxyalkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂C(O)NR_(x)R_(x),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(O)₂OH,—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₃ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₃NR_(x)R_(x),—(CH₂)₁₋₂C(O)N(CH₂CH₃)(CH₂)₁₋₃NR_(x)R_(x), —(CH₂)₀₋₂S(O)₂(C₁₋₄ alkyl),—(CH₂)₀₋₂S(O)₂(C₁₋₃ fluoroalkyl), —(CH₂)₀₋₂S(O)₂NR_(x)R_(x),—C(O)C(O)OH, —C(O)C(O)NR_(y)R_(y), or—C(O)C(O)NR_(y)(CR_(x)R_(x))₁₋₂NR_(y)R_(y);L₁ is a bond, —(CR_(x)R_(x))₁₋₂—, —(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,—(CR_(x)R_(x))₁₋₂O—, —CR_(x)R_(x)C(O)—,—(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₀₋₁—,—CR_(x)R_(x)C(O)NR_(x)(CR_(x)R_(x))₀₋₄, —C(O)(CR_(x)R_(x))₀₋₃—,—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₀₋₂—,—C(O)(CR_(x)R_(x))₀₋₂N(C₁₋₂ hydroxyalkyl)(CR_(x)R_(x))₀₋₂—,—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,—C(O)(CR_(x)R_(x))₁₋₂C(O)NR_(x)—,—(CR_(x)R_(x))₀₋₂C(O)NR_(x)(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,—(CR_(x)R_(x))₀₋₂C(O)N(C₁₋₂ hydroxyalkyl)(CR_(x)R_(x))₁₋₂—,—C(O)(CR_(x)R_(x))₀₋₁O—, —C(O)(CR_(x)R_(x))₁₋₂NHS(O)₂—,—C(O)CR_(x)(NH₂)CR_(x)R_(x)—, —C(O)C(O)(CR_(x)R_(x))₀₋₂—,—C(O)NR_(x)(CR_(x)R_(x))₁₋₂—, or —S(O)₂—;A is 2-oxa-6-azaspiro[3,3]heptanyl, 4-oxaspiro[2.5]octanyl,7-azaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl,8-oxa-3-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl,adamantanyl, azepanyl, azetidinyl, C₃₋₆ cycloalkyl, diazepanyl,dihydroinonyl, dihydropyrimidinonyl, dioxidothiadiazinanyl,dioxidoisothiazolidinyl, dioxidothiazinanyl, dioxotetrahydrothiophenyl,dioxotetrahydrothiopyranyl, dioxothiomorpholinyl, furanyl, imidazolyl,imidazolidinonyl, indolyl, isoquinolinyl, isoxazolyl, morpholinyl,morpholinonyl, naphthalenyl, octahydrocyclopenta[b]pyranyl,oxazolidinonyl, oxadiazolyl, oxetanyl, oxazolyl, phenyl, piperidinyl,piperidinonyl, piperazinyl, piperazinonyl, pyrazinyl, pyrazolyl,pyridazinonyl, pyridinonyl, pyridinyl, pyrimidinyl, pyrrolidinonyl,pyrrolidinyl, pyrrolyl, quinolinyl, quinolizinonyl, tetrahydrofuranyl,tetrahydropyranyl, tetrazolyl, thiadiazolyl, thiazolyl, or triazolyl,each substituted with -L₂-R_(a) and zero to 4 R_(b);L₂ is a bond or —CR_(x)R_(x)—;

R_(a) is:

(a) H, F, Cl, —CN, —OH, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₅ hydroxyalkyl,—(CH₂)₀₋₄O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₃NR_(y)R_(y),—(CR_(x)R_(x))₁₋₃C(O)NR_(y)R_(y), —O(C₁₋₃ fluoroalkyl),—S(O)₂NR_(x)R_(x), —O(CR_(x)R_(x))₁₋₃NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl),—NR_(x)R_(x), —NR_(x)(C₁₋₄ alkyl), —NR_(x)C(O)(C₁₋₄ alkyl),—(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(C₁₋₅ alkyl), —C(O)(C₁₋₃ fluoroalkyl),—C(O)O(C₁₋₄ alkyl), —C(O)NH(C₁₋₃ cyanoalkyl), —C(O)NR_(y)R_(y),—C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃ alkyl);(b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein each cycloalkylis substituted with zero to 2 substituents independently selected from—OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkyl, and —C(O)O(C₁₋₃alkyl); or(c) A₁, —CH₂A₁, —C(O)A₁, —NR_(x)A₁, or —C(O)NR_(x)A₁, wherein A₁ isfuranyl, imidazolyl, indolyl, isoxazolyl, morpholinyl,octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl,piperazinyl, piperidinyl, pyrazolyl, pyridinyl, pyrimidinyl,pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl,thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted withzero to three substituents independently selected from —OH, C₁₋₃ alkyl,C₁₋₃ hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃ alkyl), —NR_(x)R_(x),phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl), and—CH₂CH₂(pyrrolidinyl);each R_(b) is independently F, —CH₃, —CF₃, or —OCH₃;each R_(x) is independently H or —CH₃;each R_(y) is independently H or C₁₋₆ alkyl;R_(z) is H, C₁₋₂ alkyl, or C₁₋₂ fluoroalkyl;each R₄ is independently F, —OH, C₁₋₂ alkyl, or —OCH₃; or two R₄attached to the samecarbon atom form ═O;each R₅ is independently F, Cl, —CN, C₁₋₂ alkyl, C₁₋₂ fluoroalkyl, or—OCH₃;m is zero, 1, 2, 3, or 4;n is zero, 1, or 2; andp is zero, 1, 2, 3, or 4.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₁ is H, Cl, —CN, C₁₋₄ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃hydroxy-fluoroalkyl, C₃₋₆ cycloalkyl, —CH₂(C₃₋₆ cycloalkyl), ortetrahydropyranyl; and R₂, R₃, R₄, R₅, m, n, and p are defined in thefirst aspect or the second aspect. Included in this embodiment arecompounds in which R₁ is H, Cl, —CN, C₁₋₄ alkyl, or C₁₋₂ fluoroalkyl.Also included are compounds in which R₁ is —CH₂CH₃, —CH(CH₃)₂, or—CH₂CHF₂; and compounds in which R₁ is —CH(CH₃)₂. Also included arecompounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein each R₂ is independently F, Cl, —CN, —OH, C₁₋₃ alkyl, —CD₃, C₁₋₂fluoroalkyl, C₁₋₃ hydroxyalkyl, C₁₋₂ cyanoalkyl, C₁₋₃ aminoalkyl, C₁₋₄alkoxy, C₁₋₂ fluoroalkoxy, —O(CH₂)₁₋₂OH, —(CH₂)₁₋₄O(C₁₋₃ alkyl),—O(CH₂)₁₋₂OC(O)(C₁₋₃ alkyl), —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃ alkyl),—C(O)NR_(y)R_(y), —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄hydroxyalkyl), —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), C₃₋₆cycloalkyl, —NR_(x)C(O)(C₁₋₃ alkyl), —NR_(x)(CH₂-cyclopropyl), C₃₋₆cycloalkyl, morpholinyl, dioxothiomorpholinyl, methylpiperidinyl,methylpiperazinyl, amino-oxadiazolyl, imidazolyl, triazolyl, or—C(O)(thiazolyl); and R₁, R₃, R₄, R₅, R_(x), R_(y), m, n, and p aredefined in the first aspect or the second aspect. Included in thisembodiment are compounds in which each R₂ is independently F, Cl, —CN,C₁₋₃ alkyl, —CD₃, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl, C₁₋₂ cyanoalkyl,C₁₋₄ alkoxy, C₁₋₂ fluoroalkoxy, —O(CH₂)₁₋₂OH, —(CH₂)₁₋₄O(C₁₋₃ alkyl),—O(CH₂)₁₋₂OC(O)(C₁₋₃ alkyl), —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl),—NR_(y)(C₁₋₄ hydroxyalkyl), —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆cycloalkyl), C₃₋₆ cycloalkyl, morpholinyl, dioxothiomorpholinyl, ormethylpiperazinyl. Also included in this embodiment are compounds inwhich each R₂ is independently F, Cl, —CN, —CH₃, —CH₂CH₃, —CH(CH₃)₂,—CD₃, —CF₃, —CH₂CN, —CH₂OH, —CH₂CH₂OH, —CH(CH₃)OH, —C(CH₃)₂OH,—OCH₂CH₂OH, —OCH₃, —OCH₂CH₃, —OCH₂CH(CH₃)₂, —OCHF₂, —CH₂OCH₃,—CH₂OCH₂CH₃, —OCH₂CH₂OC(O)CH₃, —NH₂, —NH(CH₂CH₃), —NH(CH₂CF₃),—NH(CH₂C(CH₃)₂OH), —NHCH₂(phenyl), —NHS(O)₂(cyclopropyl), cyclopropyl,morpholinyl, dioxothiomorpholinyl, or methylpiperazinyl.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein each R₂ is independently halo, —CN, C₁₋₃ alkyl, —CD₃, C₁₋₂fluoroalkyl, C₁₋₂ cyanoalkyl, C₁₋₃ hydroxyalkyl, —O(CH₂)₁₋₂OH,—(CH₂)₀₋₄O(C₁₋₄ alkyl), C₁₋₃ fluoroalkoxy, —O(CH₂) and R₁, R₃, R₄, R₅,R_(x), R_(y), m, n, and p are defined in the first aspect or the secondaspect. Included in this embodiment are compounds in which ₂OC(O)(C₁₋₃alkyl), —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄hydroxyalkyl), —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), C₃₋₆cycloalkyl, morpholinyl, dioxothiomorpholinyl, or methylpiperazinyl; andR₁, R₃, R₄, R₅, R_(x), R_(y), m, n, and p are defined in the firstaspect or the second aspect.

Included in this embodiment are compounds in which each R₂ isindependently F, Cl, —CN, —OH, C₁₋₃ alkyl, —CD₃, C₁₋₂ fluoroalkyl, C₁₋₂cyanoalkyl, C₁₋₃ hydroxyalkyl, —O(CH₂)₁₋₂OH, —O(C₁₋₄ alkyl), C₁₋₂fluoroalkoxy, —(CH₂)₁₋₄O(C₁₋₃ alkyl), —O(CH₂)₁₋₂ OC(O)(C₁₋₃ alkyl),—NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄ hydroxyalkyl),—NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), C₃₋₆ cycloalkyl,morpholinyl, dioxothiomorpholinyl, or methylpiperazinyl. Also includedare compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₂ is F, Cl, —CN, C₁₋₂ alkyl, —CD₃, —CF₃, —CH₂OH, —C(CH₃)₂OH,—OCH₃, —CH₂OCH₃, —OCH₂CH₃, cyclopropyl, or morpholinyl; and R₁, R₃, R₄,R₅, m, n, and p are defined in the first aspect or the second aspect.Included in this embodiment are compounds in which each R₂ isindependently —CH₃ or —OCH₃. Also included are compounds in which m iszero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is -L₁-A; and R₁, R₂, R₄, R₅, L₁, and A are defined in thefirst aspect or the second aspect. Included in this embodiment arecompounds in which L₁ is a bond, —(CR_(x)R_(x))₁₋₂—,—(CR_(x)R_(x))₁₋₂CR_(x)(OH)—, —(CR_(x)R_(x))₁₋₂O—, —CR_(x)R_(x)C(O)—,—(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₀₋₁—,—CR_(x)R_(x)C(O)NR_(x)(CR_(x)R_(x))₀₋₄—, —C(O)(CR_(x)R_(x))₀₋₃—,—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₀₋₂—,—C(O)(CR_(x)R_(x))₀₋₂N(C₁₋₂ hydroxyalkyl)(CR_(x)R_(x))₀₋₂—,—C(O)(CR_(x)R_(x))₁₋₂C(O)NR_(x)—,—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,—(CR_(x)R_(x))₀₋₂C(O)NR_(x)(CR_(x)R_(x))₁₋₂CR_(x)(OH)—,—(CR_(x)R_(x))₀₋₂C(O)N(C₁₋₂ hydroxyalkyl)(CR_(x)R_(x))₁₋₂—,—C(O)(CR_(x)R_(x))₀₋₁O—, —C(O)(CR_(x)R_(x))₁₋₂NHS(O)₂—,—C(O)CR_(x)(NH₂)CR_(x)R_(x)—, —C(O)C(O)(CR_(x)R_(x))₀₋₂—,—C(O)NR_(x)(CR_(x)R_(x))₁₋₂—, or —S(O)₂—. Also included are compounds inwhich L₁ is a bond, —CR_(x)R_(x)—, —CR_(x)R_(x)C(O)—,—CR_(x)R_(x)C(O)NR_(x)—, or —C(O)(CR_(x)R_(x))₀₋₂—. Also included arecompounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is -L₁-A; L₁ is a bond, —CR_(x)R_(x)—, —CR_(x)R_(x)C(O)—,—CR_(x)R_(x)C(O)NR_(x)—, or —C(O)(CR_(x)R_(x))₀₋₂—; A is a ring selectedfrom azetidinyl, C₃₋₆ cycloalkyl, dioxotetrahydrothiopyranyl,dioxidothiadiazinanyl, dioxidothiomorpholinyl, furanyl, imidazolyl,isoquinolinyl, morpholinyl, oxazolyl, 2-oxa-6-azaspiro[3.3]heptanyl,oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolyl,pyridinyl, pyrrolidinyl, pyrrolyl, quinolinyl, tetrahydrofuranyl,tetrahydropyranyl, tetrazolyl, thiadiazolyl, thiazolyl, and triazolyl,each substituted with -L₂-R_(a) and zero to 4 R_(b); and R₁, R₂, R₄, R₅,R_(x), L₂, R_(a) m, n, and p are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which L₂ isa bond or —CR_(x)R_(x)—; and R_(a) is (a) H, —CN, —OH, C₁₋₃ alkyl, C₁₋₂fluoroalkyl, C₁₋₃ hydroxyalkyl, —(CH₂)₁₋₂O(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₃NH₂,—(CR_(x)R_(x))₁₋₃NR_(x)(C₁₋₄ alkyl), —O(C₁₋₂ fluoroalkyl),—S(O)₂NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl), —NR_(x)R_(x), —NR_(x)(C₁₋₄alkyl), —(CR_(x)R_(x))₁₋₂C(O)OH, —C(O)OH, —C(O)(C₁₋₃ alkyl), —C(O)O(C₁₋₃alkyl), —C(O)NR_(x)(C₁₋₂ alkyl), —C(O)N(C₁₋₃ alkyl)₂,—C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃ alkyl);(b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein each cycloalkylis substituted with zero to 2 substituents independently selected from—OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkyl, and —C(O)O(C₁₋₃alkyl); or (c) A₁, —CH₂A₁, —C(O)A₁, or —C(O)NHA₁, wherein A₁ is furanyl,imidazolyl, indolyl, isoxazolyl, octahydropyrrolo[3,4-c]pyrrolyl,oxazolyl, oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazolyl,pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl,tetrahydropyranyl, thiadiazolyl, thiazolyl, thiophenyl, or triazolyl,each substituted with zero to three substituents independently selectedfrom —OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃alkyl), —NR_(x)R_(x), phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl),and —CH₂CH₂(pyrrolidinyl). Also included are compounds in which m iszero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is H, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ cyanoalkyl, C₁₋₆hydroxyalkyl, C₁₋₃ hydroxy-fluoroalkyl,—CR_(x)R_(x)CR_(x)(OH)CR_(x)═CR_(x)R_(x), —C═N(NR_(x)R_(x)),—(CR_(x)R_(x))₁₋₄O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₄O(CR_(x)R_(x))₁₋₃O(C₁₋₃alkyl), —CH₂CH(OH)CH₂O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),—(CH₂)₁₋₃C(O)OC(CH₃)₃, —(CR_(x)R_(x))₀₋₃NR_(x)R_(y),—(CR_(x)R_(x))₀₋₃NR_(x)(C₁₋₄ hydroxyalkyl), —CH₂CH(OH)CH₂NR_(x)R_(y),—C(O)H, —C(O)(C₁₋₆ alkyl), —C(O)(C₁₋₄ hydroxyalkyl), —C(O)(C₁₋₃fluoroalkyl), —C(O)(C₁₋₃ chloroalkyl), —C(O)(C₁₋₃ cyanoalkyl),—(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(CH₂)₀₋₂O(C₁₋₄ alkyl),—C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂O(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂NR_(y)R_(y),—C(O)CR_(x)R_(x)S(O)₂(C₁₋₃ alkyl), —C(O)CR_(x)R_(x)NR_(x)S(O)₂(C₁₋₃alkyl), —C(O)CR_(x)R_(x)OC(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₃NR_(y)R_(y), —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₃cyanoalkyl), —C(O)(CR_(x)R_(x))₀₋₂NR_(y)(C₁₋₆ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(C₁₋₃ fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₅ hydroxy-fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂O(C₁₋₃ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₂ alkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)(CR_(x)R_(x))₀₋₂N((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl))₂,—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CR_(x)R_(x))₁₋₃NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)C(O)NR_(x)R_(x),—C(O)(CR_(x)R_(x))₀₋₃NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₃N((CH₂)₀₋₁C(O)(C₁₋₃ alkyl))₂,—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),—C(O)(CR_(x)R_(x))₁₋₃C(O)NR_(y)R_(y), —C(O)(CR_(x)R_(x))₁₋₃S(O)₂NR_(y)R_(y), —C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CHR_(y)(CH₂OH)),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y), —CH(CN)C(O)NR_(y)R_(y),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃ fluoroalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₄ hydroxyalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃ cyanoalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(CH₂)₁₋₂O(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₄ alkyl)(C₁₋₃ hydroxyalkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂C(O)NR_(x)R_(x),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(C₁₋₃ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(O)₂OH,—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₃ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₃NR_(x)R_(x),—(CH₂)₁₋₂C(O)N(CH₂CH₃)(CH₂)₁₋₃NR_(x)R_(x), —(CR_(x)R_(x))₀₋₃S(O)₂(C₁₋₄alkyl), —(CH₂)₀₋₂S(O)₂(C₁₋₃ fluoroalkyl),—(CR_(x)R_(x))₀₋₂S(O)₂NR_(y)R_(y), —(CR_(x)R_(x))₀₋₂NR_(x)S(O)₂(C₁₋₃alkyl), —C(O)C(O)OH, —C(O)C(O)NR_(y)R_(y), or—C(O)C(O)NR_(y)(CR_(x)R_(x))₁₋₂NR_(y)R_(y); and R₁, R₂, R₄, R₅, R_(x),R_(y), m, n, and p are defined in the first aspect or the second aspect.Also included are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is H, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ cyanoalkyl, C₁₋₅hydroxyalkyl, —C═N(NR_(x)R_(x)), —(CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl),—(CR_(x)R_(x))₁₋₄O(CR_(x)R_(x))₁₋₃O(C₁₋₃ alkyl), —CH₂CH(OH)CH₂O(C₁₋₃alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl), —(CH₂)₁₋₃C(O)OC(CH₃)₃,—(CR_(x)R_(x))₀₋₃NR_(x)R_(y), —(CR_(x)R_(x))₀₋₃NR_(x)(C₁₋₄hydroxyalkyl), —CH₂CH(OH)CH₂NR_(x)R_(y), —C(O)(C₁₋₆ alkyl), —C(O)(C₁₋₄hydroxyalkyl), —C(O)(C₁₋₃ fluoroalkyl), —C(O)(C₁₋₃ chloroalkyl),—C(O)(C₁₋₃ cyanoalkyl), —(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(CH₂)₀₋₂O(C₁₋₄alkyl), —C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂O(C₁₋₃ alkyl),—C(O)(CH₂)₀₋₂O(CH₂)₁₋₂HR_(y)R_(y), —C(O)CR_(x)R_(x)S(O)₂(C₁₋₂ alkyl),—C(O)CR_(x)R_(x)NR_(x)S(O)₂(C₁₋₂ alkyl), —C(O)CR_(x)R_(x)OC(O)(C₁₋₃alkyl), —C(O)(CR_(x)R_(x))₀₋₂NR_(y)R_(y),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(C₁₋₂ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(y)(C₁₋₆ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(C₁₋₃ fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₅ hydroxy-fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂O(C₁₋₃ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₂ alkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CR_(x)R_(x))₁₋₃NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)C(O)NR_(x)R_(x),—C(O)(CR_(x)R_(x))₀₋₃NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CHR_(y)(CH₂OH)),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃fluoroalkyl), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₄ hydroxyalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(C₁₋₃ cyanoalkyl), —CH(CN)C(O)NR_(y)R_(y),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(CH₂)₁₋₂O(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₄ alkyl)(C₁₋₃ hydroxyalkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂C(O)NR_(x)R_(x),—(CH₂)₁₋₂S(O)₂NR_(x)(CH₂)₁₋₂S(C₁₋₂ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(O)₂OH,—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₃ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₃NR_(x)R_(x),—(CH₂)₁₋₂C(O)N(CH₂CH₃)(CH₂)₁₋₃NR_(x)R_(x), —(CR_(x)R_(x))₁₋₃S(O)₂(C₁₋₄alkyl), —(CH₂)₀₋₂S(O)₂(C₁₋₃ fluoroalkyl), —(CH₂)₁₋₂S(O)₂NR_(y)R_(y),—C(O)C(O)OH, —C(O)C(O)NR_(y)R_(y), or—C(O)C(O)NR_(y)(CR_(x)R_(x))₁₋₂NR_(y)R_(y); and R₁, R₂, R₄, R₅, m, n,and p are defined in the first aspect or the second aspect. Alsoincluded are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is —C(O)CH₂(2-oxa-6-azaspiro[3.3]heptanyl),—C(O)CH₂(piperazinonyl), —C(O)CH₂(piperazinyl), —C(O)CH₂(piperidinyl),—C(O)CH₂(pyrimidinyl), —C(O)CH₂(pyrrolidinyl),—C(O)CH₂(tetrahydropyranyl), —C(O)CH₂(tetrazolyl), —C(O)CH₂(thiazolyl),—C(O)CH₂CH₂(azepanyl), —C(O)CH₂CH₂(azetidinyl),—C(O)CH₂CH₂(dioxothiomorpholinyl), —C(O)CH₂CH₂(morpholinyl),—C(O)CH₂CH₂(piperidinonyl), —C(O)CH₂CH₂(piperidinyl),—C(O)CH₂CH₂(pyrrolidinonyl), —C(O)CH₂CH₂(pyrrolidinyl),—C(O)CH₂CH(CH₃)(oxetanyl), —C(O)NH(piperidinyl), —C(O)NH(pyrrolidinyl,—C(O)CH₂NH(cyclopropyl), —C(O)CH₂NH(cyclobutyl), —C(O)CH₂NH(cyclohexyl),—C(O)CH₂NH(oxetanyl), —C(O)CH₂N(CH₃)(cyclopropyl),—C(O)CH₂N(CH₃)(cyclohexyl), —C(O)CH₂CH₂NH(cyclopentyl),—C(O)CH₂CH₂NH(cyclohexyl), —C(O)CH₂CH₂N(CH₃)(cyclohexyl),—C(O)CH₂N(CH₂CH₂OH)(cyclopropyl), —C(O)CH₂CH₂N(CH₂CH₂OH)(cyclopropyl),—C(O)CH₂CH₂NH(CH₂(cyclopropyl)), —C(O)CH₂CH₂NH(CH₂(tetrahydrofuranyl)),—C(O)CH₂NH(CH₂(cyclopropyl)), —C(O)CH₂NH(CH₂(cyclohexyl)),—C(O)CH₂NH(CH₂(tetrahydrofuranyl)), —C(O)NH(CH₂(piperidinyl)),—C(O)NH(CH₂(pyrrolidinyl)), —C(O)NH(CH₂CH₂(morpholinyl)),—C(O)NH(CH₂CH₂(piperazinyl)), —C(O)NH(CH₂CH₂(piperidinyl)),—C(O)NH(CH₂CH₂(pyrrolidinyl)), —C(O)O(azetidinyl), —C(O)O(piperidinyl),—C(O)O(pyrrolidinyl), —C(O)OCH₂(azetidinyl), —C(O)OCH₂(piperidinyl),—C(O)OCH₂(pyrrolidinyl), —C(O)OCH₂CH₂(dioxothiomoropholinyl),—C(O)OCH₂CH₂(imidazolyl), —C(O)OCH₂CH₂(morpholinyl),—C(O)OCH₂CH₂(piperazinyl), —C(O)OCH₂CH₂(piperidinyl),—C(O)OCH₂CH₂(pyrrolidinyl), —CH₂(cyclopropyl),—CH₂(dioxotetrahydrothiopyranyl), —CH₂(imidazolyl), —CH₂(isoxazolyl),—CH₂(morpholinyl), —CH₂(oxadiazolyl), —CH₂(oxazolyl), —CH₂(oxetanyl),—CH₂(phenyl), —CH₂(pyrazinyl), —CH₂(pyrazolyl), —CH₂(pyridazinyl),—CH₂(pyrimidinyl), —CH₂(tetrazolyl), —CH₂(thiadiazolyl),—CH₂(thiazolyl), —CH₂(triazolonyl), —CH₂(triazolyl),—CH(CH₃)(pyrazolyl), —CH(CH₃)(pyridazinyl), —CH(CH₃)(pyrimidinyl),—CH₂CH₂(dioxoisothiazolidinyl), —CH(CN)(oxetanyl),—CH(CH₃)CH₂S(O)₂(morpholinyl), —CH(CH₃)CH₂S(O)₂(piperidinyl),—CH₂C(O)(morpholinyl), —CH₂C(O)(2-oxa-6-azaspiro[3.3]heptanyl),—CH₂C(O)(azetidinyl), —CH₂C(O)(dioxidothiadiazinanyl),—CH₂C(O)(dioxidothiazolidinyl), —CH₂C(O)(dioxidothiomorpholinyl),—CH₂C(O)(dioxothiomorpholinyl), —CH₂C(O)(2-oxa-6-azaspiro[3.3]heptanyl),—CH₂C(O)(piperazinonyl), —CH₂C(O)(piperazinyl), —CH₂C(O)(piperidinyl),—CH₂C(O)(pyrrolidinyl), —CH₂C(O)NHCH(CH₂CH₂OH)(cyclopropyl),—CH₂C(O)N(CH₂CH₂OH)(cyclopropyl), —CH₂C(O)N(CH₃)(cyclopropyl),—CH₂C(O)N(CH₃)(tetrahydrofuranyl), —CH₂C(O)N(CH₃)(tetrahydropyranyl),—CH₂C(O)N(CH₃)CH₂CH₂(cyclopentyl), —CH₂C(O)N(CH₃)CH₂CH₂(pyrazolyl),—CH₂C(O)NH(azetidinyl), —CH₂C(O)NH(CH₂(oxetanyl)),—CH₂C(O)NH(cyclobutyl), —CH₂C(O)NH(cyclopropyl), —CH₂C(O)NH(oxetanyl),—CH₂C(O)NH(tetrahydropyranyl), —CH₂CH₂S(O)₂(morpholinyl), or—CH₂CH₂S(O)₂(phenyl); and R₁, R₂, R₄, R₅, m, n, and p are defined in thefirst aspect or the second aspect. Also included are compounds in whichm is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is H, C₁₋₅ alkyl, C₂₋₃ fluoroalkyl, C₁₋₃ cyanoalkyl, C₂₋₅hydroxyalkyl, —CH₂CH₂OCH₃, —CH₂N(CH₃)₂, —CH₂CH₂NH(CH₃), —C═N(NH₂),—C(O)CH₃, —C(O)CH(CH₂CH₃)₂, —C(O)CH₂CF₃, —C(O)CH₂CH₂OH, —C(O)CH(CH₃)OH,—C(O)CH₂CH(CH₃)OH, —C(O)CH₂C(CH₃)₂OH, —C(O)CH₂CN, —C(O)CH₂CH₂CN,—C(O)OC(CH₃)₃, —C(O)CH₂OCH₃, —C(O)CH₂CH₂OCH₃, —C(O)OCH₂CH₂NH₂,—C(O)OCH₂CH₂N(CH₃)₂, —C(O)OCH₂CH₂N(CH₂CH₃)₂, —C(O)CH₂S(O)₂CH₃,—C(O)CH₂CH₂S(O)₂CH₃, —C(O)CH₂NHS(O)₂CH₃, —C(O)NH(CH₂C(CH₃)₃),—C(O)CH₂NH(CH₃), —C(O)CH₂NH(CH₂CH₃), —C(O)CH₂NH(CH₂CH₂CH₃),—C(O)CH₂NH(CH₂CH₂CH₃), —C(O)CH₂NH(CH(CH₃)₂), —C(O)CH₂NH(CH₂CH(CH₃)₂),—C(O)CH₂NH(C(CH₃)₃), —C(O)CH₂N(CH₃)₂, —C(O)CH₂N(CH₃)(CH₂CH₃),—C(O)CH₂N(CH₃)(CH₂CH₂CH₃), —C(O)CH₂N(CH₃)(CH(CH₃)₂),—C(O)CH₂N(CH₃)(CH₂CH(CH₃)₂), —C(O)CH₂N(CH₂CH₃)₂, —C(O)CH₂CH₂NH(CH₃),—C(O)CH₂CH₂NH(CH₂CH₃), —C(O)CH₂CH₂NH(CH₂CH₂CH₃),—C(O)CH₂CH₂NH(CH(CH₃)₂), —C(O)CH₂CH₂NH(CH₂C(CH₃)₃), —C(O)CH₂CH₂N(CH₃)₂,—C(O)CH₂CH₂N(CH₃)(CH₂CH₃), —C(O)CH₂CH₂N(CH₃)(CH₂CH₂CH₃),—C(O)CH₂CH₂N(CH₃)(CH(CH₃)₂), —C(O)CH(CH₃)NH(CH₃), —C(O)CH₂NH(CH₂CN),—C(O)CH₂N(CH₃)(CH₂CH₂CN), —C(O)CH₂NH(CH₂C(O)NH₂),—C(O)CH₂N(CH₃)(CH₂C(O)N(CH₃)₂), —C(O)CH₂CH₂NH(CH₂C(O)NH₂),—C(O)CH₂CH₂N(CH₃)CH₂C(O)N(CH₃)₂. —C(O)CH₂NH(CH₂CH₂OH),—C(O)CH₂N(CH₃)(CH₂CH₂OH), —C(O)CH₂CH₂NH(CH₂CH₂OH),—C(O)CH₂CH₂N(CH₃)(CH₂CH₂OH), —C(O)CH₂NH(CH₂CH₂F), —C(O)CH₂NH(CH₂CF₃),—C(O)CH₂CH₂NH(CH₂CH₂F), —C(O)CH₂NH(CH₂CH₂OCH₃),—C(O)CH₂N(CH₃)(CH₂CH₂OCH₃), —C(O)CH₂CH₂NH(CH₂CH₂OCH₃),—C(O)CH₂CH₂N(CH₃)(CH₂CH₂OCH₃), —C(O)CH₂N(CH₂CH₂OCH₃)₂,—C(O)CH₂CH₂CH₂S(O)₂NH₂, —CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)₂,—CH₂C(O)NH(CH₂CH₃), —CH₂C(O)N(CH₃)(CH₂CH₃), —CH₂C(O)N(CH₂CH₃)₂,—CH₂C(O)NH(CH₂CH₂CH₃), —CH₂C(O)NH(CH(CH₃)₂), —CH(CN)C(O)N(CH₃)₂,—CH₂C(O)NH(CH₂CH₂CF₃), —CH₂C(O)N(CH₃)(CH₂CH₂OH),—CH₂C(O)N(CH₃)(CH₂CH₂OH), —CH₂C(O)N(CH₂CH₃)(CH₂CH₂OH),—CH₂C(O)N(CH₂CH₂CH₃)(CH₂CH₂OH), —CH₂C(O)N(CH₃)(CH₂CH₂CH₂OH),—CH₂C(O)NH(CH₂C(CH₃)₂OH), —CH₂C(O)N(CH₂CH(CH₃)CH₂CH₃)(CH₂CH₂OH),—CH₂C(O)NH(CH₂CH₂CN), —CH₂C(O)N(CH₃)(CH₂CH₂CN),—CH₂C(O)N(CH₃)(CH₂CH₂OCH₃), —CH(CH₃)CH₂S(O)₂(CH₂CH₂CH₂CH₃),—CH₂CH₂S(O)₂NH₂, —CH₂CH₂S(O)₂NH(CH₃), —CH₂CH₂S(O)₂N(CH₃)₂,—CH(CH₃)CH₂S(O)₂N(CH₂CH₃)₂, —CH₂CH₂NHS(O)₂CH₃, —CH₂CH₂N(CH₃)S(O)₂CH₃,—CH₂C(O)NH(CH₂CH₂SCH₃), —C(O)NH(CH₂CH₂NH₂), —C(O)N(CH₃)CH₂CH₂NH₂,—C(O)NH(CH₂CH₂N(CH₃)₂), —C(O)NH(CH₂CH₂CH₂NH₂), —CH₂CH₂S(O)₂CH₃,—CH₂CH₂CH₂S(O)₂CH₃, or —CH(CH₃)CH₂S(O)₂CH₃; and R₁, R₂, R₄, R₅, m, n,and p are defined in the first aspect or the second aspect. Alsoincluded are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein each R₄ is independently F, —OH, C₁₋₂ alkyl, or —OCH₃; or two R₄attached to the same carbon atom form ═O; and R₁, R₂, R₃, R₅, m, n and pare defined in the first aspect. Included in this embodiment arecompounds in which each R₄ is independently F, —CH₃, or —OCH₃. Alsoincluded are compounds in which n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein each R₅ is independently F, Cl, —CN, —CH₃, —CF₃, or —OCH₃; andR₁, R₂, R₃, R₄, m, n and p are defined in the first aspect. Included inthis embodiment are compounds in which each R₅ is independently F, —CN,—CH₃, or —CF₃. Also included are compounds in which m is zero. Further,included are compounds in which m is zero and n is 1.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein m is 2, 3, or 4; two R₄, each attached to a different carbonatom adjacent to the nitrogen atom in the piperidinyl ring, can form a—CH₂CH₂— bridge; and R₁, R₂, R₃, R₅, m, n, and p are defined in thefirst aspect. The compounds of this embodiment have the structure ofFormula (Ia):

Included in this embodiment are compounds in which R₁ is —CH(CH₃)₂; eachR₂ is —CH₃; R₃ is —CH₂CN, —CH₂C(O)N(CH₃)₂, or —CH₂CH₂S(O)₂CH₃; m is 2; nis zero, and p is zero, 1, or 2. Also included in this embodiment arecompounds selected from2-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)acetonitrile(981);2-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)-N,N-dimethylacetamide(982-983); and6-(3-isopropyl-5-(8-(2-(methylsulfonyl)ethyl)-8-azabicyclo[3.2.1]octan-3-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(984-985).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein: R₁ is H, Cl, —CN, C₁₋₄ alkyl, or C₁₋₂ fluoroalkyl; each R₂ isindependently F, Cl, —CN, —OH, C₁₋₃ alkyl, —CD₃, C₁₋₂ fluoroalkyl, C₁₋₂cyanoalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl, —O(CH₂)₁₋₂OH, —O(C₁₋₄alkyl), C₁₋₂ fluoroalkoxy, —(CH₂)₁₋₄O(C₁₋₃ alkyl), —O(CH₂)₁₋₂OC(O)(C₁₋₃alkyl), —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃ alkyl), —C(O)NR_(y)R_(y),—NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄ hydroxyalkyl),—NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), —NR_(x)C(O)(C₁₋₃alkyl), —NR_(x)(CH₂-cyclopropyl), C₃₋₆ cycloalkyl, morpholinyl,dioxothiomorpholinyl, methylpiperidinyl, methylpiperazinyl,amino-oxadiazolyl, imidazolyl, triazolyl, or —C(O)(thiazolyl); R₃ is:(a) -L₁-A; or (b) H, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ cyanoalkyl, C₁₋₅hydroxyalkyl, —C═N(NR_(x)R_(x)), —(CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl),—(CR_(x)R_(x))₁₋₄O(CR_(x)R_(x))₁₋₃O(C₁₋₃ alkyl), —CH₂CH(OH)CH₂O(C₁₋₃alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl), —(CH₂)₁₋₃C(O)OC(CH₃)₃,—(CR_(x)R_(x))₀₋₃NR_(x)R_(y), —(CR_(x)R_(x))₀₋₃NR_(x)(C₁₋₄hydroxyalkyl), —CH₂CH(OH)CH₂NR_(x)R_(y), —C(O)(C₁₋₆ alkyl), —C(O)(C₁₋₄hydroxyalkyl), —C(O)(C₁₋₃ fluoroalkyl), —C(O)(C₁₋₃ chloroalkyl),—C(O)(C₁₋₃ cyanoalkyl), —(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(CH₂)₀₋₂O(C₁₋₄alkyl), —C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂O(C₁₋₃ alkyl),—C(O)(CH₂)₀₋₂O(CH₂)₁₋₂HR_(y)R_(y), —C(O)CR_(x)R_(x)S(O)₂(C₁₋₂ alkyl),—C(O)CR_(x)R_(x)NR_(x)S(O)₂(C₁₋₂ alkyl), —C(O)CR_(x)R_(x)OC(O)(C₁₋₃alkyl), —C(O)(CR_(x)R_(x))₀₋₂NR_(y)R_(y),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(C₁₋₂ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(y)(C₁₋₆ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(C₁₋₃ fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₅ hydroxy-fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂O(C₁₋₃ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₂ alkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CR_(x)R_(x))₁₋₃NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)C(O)NR_(x)R_(x),—C(O)(CR_(x)R_(x))₀₋₃NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),—C(O)(CR_(x)R_(x))₀₋₂NR_(x)(CHR_(y)(CH₂OH)),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃fluoroalkyl), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₄ hydroxyalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(C₁₋₃ cyanoalkyl), —CH(CN)C(O)NR_(y)R_(y),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(CH₂)₁₋₂O(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₄ alkyl)(C₁₋₃ hydroxyalkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂C(O)NR_(x)R_(x),—(CH₂)₁₋₂S(O)₂NR_(x)(CH₂)₁₋₂S(C₁₋₂ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(O)₂OH,—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₃ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₃NR_(x)R_(x),—(CH₂)₁₋₂C(O)N(CH₂CH₃)(CH₂)₁₋₃NR_(x)R_(x), —(CR_(x)R_(x))₁₋₃S(O)₂(C₁₋₄alkyl), —(CH₂)₀₋₂S(O)₂(C₁₋₃ fluoroalkyl), —(CH₂)₁₋₂S(O)₂NR_(y)R_(y),—C(O)C(O)OH, —C(O)C(O)NR_(y)R_(y), or—C(O)C(O)NR_(y)(CR_(x)R_(x))₁₋₂NR_(y)R_(y); L₁ is a bond, —CR_(x)R_(x)—,—CR_(x)R_(x)C(O)—, —CR_(x)R_(x)C(O)NR_(x)—, or —C(O)(CR_(x)R_(x))₀₋₂—; Ais a ring selected from azetidinyl, C₃₋₆ cycloalkyl,dioxotetrahydrothiopyranyl, dioxidothiadiazinanyl,dioxidothiomorpholinyl, furanyl, imidazolyl, isoquinolinyl, morpholinyl,oxazolyl, 2-oxa-6-azaspiro[3.3]heptanyl, oxetanyl, phenyl, piperazinyl,piperidinyl, pyrazinyl, pyrazolyl, pyridinyl, pyrrolidinyl, pyrrolyl,quinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrazolyl,thiadiazolyl, thiazolyl, and triazolyl, each substituted with -L₂-R_(a)and zero to 4 R_(b); L₂ is a bond or —CR_(x)R_(x)—; R_(a) is: (a) H,—CN, —OH, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl,—(CH₂)₁₋₂O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl),—(CR_(x)R_(x))₁₋₃NH₂, —(CR_(x)R_(x))₁₋₃NR_(x)(C₁₋₄ alkyl), —O(C₁₋₂fluoroalkyl), —S(O)₂NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl), —NR_(x)R_(x),—NR_(x)(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₂C(O)OH, —C(O)OH, —C(O)(C₁₋₃alkyl), —C(O)O(C₁₋₃ alkyl), —C(O)NR_(x)(C₁₋₂ alkyl), —C(O)N(C₁₋₃alkyl)₂, —C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃alkyl); (b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein eachcycloalkyl is substituted with zero to 2 substituents independentlyselected from —OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkyl, and—C(O)O(C₁₋₃ alkyl); or (c) A₁, —CH₂A₁, —C(O)A₁, or —C(O)NHA₁, wherein A₁is furanyl, imidazolyl, indolyl, isoxazolyl,octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl,piperazinyl, piperidinyl, pyrazolyl, pyridinyl, pyrimidinyl,pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl,thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted withzero to three substituents independently selected from —OH, C₁₋₃ alkyl,C₁₋₃ hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃ alkyl), —NR_(x)R_(x),phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl), and—CH₂CH₂(pyrrolidinyl); each R₄ is independently F, —OH, C₁₋₂ alkyl, or—OCH₃; or two R₄ attached to the same carbon atom form ═O; R₅ is F, Cl,—CN, C₁₋₂ alkyl, or —OCH₃; each R_(b) is independently —CH₃ or —CF₃;each R_(x) is independently H or —CH₃; each R_(y) is independently H orC₁₋₅ alkyl; m is zero, 1, or 2; n is zero or 1; and p is zero, 1, or 2.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein: R₁ is —CH(CH₃)₂; each R₂ is independently —CH₃, —OCH₃, or—CH₂OCH₃; R₃ is H, —CH(CH₃)₂, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂CN,—CH₂CH₂CN, —CH₂CH₂CH₂CN, —CH₂C(CH₃)₂OH, —C(O)CH₃, —C(O)CH(CH₂CH₃)₂,—C(O)CH₂OCH₃, —C(O)CH₂CH₂OCH₃, —C(O)CH₂CH(CH₃)OH, —C(O)CH₂CN,—C(O)CH₂CH₂CN, —C(O)CH(CH₃)NH(CH₃), —C(O)CH₂NH(CH₃), —C(O)CH₂N(CH₃)₂,—C(O)CH₂NHCH₂CH₂CH₃, —C(O)CH₂NHCH(CH₃)₂, —C(O)CH₂NHC(CH₃)₃,—C(O)CH₂N(CH₃)CH(CH₃)₂, —C(O)CH₂NHCH₂CH₂OCH₃, —CH₂C(O)NH₂,—CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)CH₂CH₃, —CH₂C(O)NHCH₂CH₂CH₃,—CH₂C(O)NH(CH(CH₃)₂), —CH₂C(O)N(CH₃)₂, —CH₂C(O)N(CH₂CH₃)₂,—CH₂CH₂S(O)₂CH₃, —CH₂CH₂S(O)₂NH₂, —CH₂C(O)NH(cyclobutyl),—CH₂C(O)NH(cyclopropyl), —CH₂C(O)NH(methyloxetanyl),—CH₂C(O)N(CH₃)(cyclopropyl), oxetanyl, tetrahydropyranyl,dioxotetrahydrothiopyranyl, —CH₂(oxazolyl), —CH₂(pyrazolyl),—CH₂(tetrazolyl), —CH₂(triazolyl), —CH₂(methyltriazolyl),—CH₂C(O)(2-oxa-6-azaspiro[3.3]heptanyl), —CH₂C(O)(azetidinyl),—CH₂C(O)(dioxidothiadiazinanyl), —CH₂C(O)(dioxidothiomorpholinyl),—CH₂C(O)(morpholinyl), —CH₂C(O)(methoxyethylpiperazinyl),—CH₂C(O)(piperidinyl), —CH₂C(O)(hydroxypiperidinyl),—CH₂C(O)(pyrrolidinyl), —CH₂C(O)(hydroxypyrrolidinyl),—C(O)(azetidinyl), —C(O)(methylcyclopropyl), —C(O)(methyloxetanyl), or—C(O)CH₂(morpholinyl); m is zero; n is zero; and p is zero, 1 or 2.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₁ is H, Cl, —CN, C₁₋₄ alkyl, C₁₋₂ fluoroalkyl, C₁₋₂hydroxy-fluoroalkyl, C₃₋₆ cycloalkyl, —CH₂(C₃₋₆ cycloalkyl), —C(O)O(C₁₋₂alkyl), or tetrahydropyranyl; and R₂, R₃, R₄, R₅, m, n, and p aredefined in the first aspect. Included in this embodiment are compoundsin which R₁ is H, Cl, —CN, C₁₋₄ alkyl, or C₁₋₂ fluoroalkyl. Alsoincluded in this embodiment are compounds in which R₁ is —CH(CH₃)₂. Alsoincluded are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein each R₂ is independently F, Cl, —CN, —OH, C₁₋₃ alkyl, C₁₋₂fluoroalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl, —(CH₂)₀₋₂O(C₁₋₂ alkyl),C₁₋₃ fluoroalkoxy, or C₃₋₆ cycloalkyl; and R₁, R₃, R₄, R₅, m, n, and pare defined in the first aspect. Included in this embodiment arecompounds in which each R₂ is independently F, —CN, —OH, C₁₋₂ alkyl, or—(CH₂)₀₋₁O(C₁₋₂ alkyl). Also included in this embodiment are compoundsin which each R₂ is independently —CH₃, —OCH₃, or —CH₂OCH₃. Alsoincluded are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein each R₂ is independently F, —CN, —OH, C₁₋₂ alkyl, or—(CH₂)₀₋₁O(C₁₋₂ alkyl); p is zero, 1 or 2; and R₁, R₃, R₄, R₅, m, and nare defined in the first aspect. Included in this embodiment arecompounds in which each R₂ is independently —CH₃, —OCH₃, or —CH₂OCH₃.Also included are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein the compound has one of the following structures:

Included in this embodiment are compounds in which R₁ is H, Cl, —CN,C₁₋₄ alkyl, or C₁₋₂ fluoroalkyl. Also included in this embodiment arecompounds in which R₁ is —CH(CH₃)₂. Also included are compounds in whichm is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is -L₁-A; and R₁, R₂, R₄, R₅, L₁, A, m, n, and p are definedin the first aspect. Included in this embodiment are compounds in whichL₁ is a bond, —CR_(x)R_(x)—, —CR_(x)R_(x)C(O)—, —CR_(x)R_(x)C(O)NR_(x)—,or —C(O)(CR_(x)R_(x))₀₋₂—; A is a ring selected from azetidinyl, C₃₋₆cycloalkyl, dioxotetrahydrothiopyranyl, dioxidothiazinanyl,dioxidothiomorpholinyl, furanyl, imidazolyl, isoquinolinyl, morpholinyl,oxazolyl, 2-oxa-6-azaspiro[3.3]heptanyl, oxetanyl, phenyl, piperazinyl,piperidinyl, pyrazinyl, pyrazolyl, pyridinyl, pyrrolidinyl, pyrrolyl,quinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrazolyl,thiadiazolyl, thiazolyl, and triazolyl, each substituted with -L₂-R_(a)and zero to 4 R_(b); L₂ is a bond or —CR_(x)R_(x)—; R_(a) is (a) H, —CN,—OH, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl, —(CH₂)₁₋₂O(C₁₋₃alkyl), —(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₃NH₂,—(CR_(x)R_(x))₁₋₃NR_(x)(C₁₋₄ alkyl), —O(C₁₋₂ fluoroalkyl),—S(O)₂NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl), —NR_(x)R_(x), —NR_(x)(C₁₋₄alkyl), —(CR_(x)R_(x))₁₋₂C(O)OH, —C(O)OH, —C(O)(C₁₋₃ alkyl), —C(O)O(C₁₋₃alkyl), —C(O)NR_(x)(C₁₋₂ alkyl), —C(O)N(C₁₋₃ alkyl)₂,—C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃ alkyl);(b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein each cycloalkylis substituted with zero to 2 substituents independently selected from—OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkyl, and —C(O)O(C₁₋₃alkyl); or (c) A₁, —CH₂A₁, —C(O)A₁, or —C(O)NHA₁, wherein A₁ is furanyl,imidazolyl, indolyl, isoxazolyl, octahydropyrrolo[3,4-c] pyrrolyl,oxazolyl, oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazolyl,pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl,tetrahydropyranyl, thiadiazolyl, thiazolyl, thiophenyl, or triazolyl,each substituted with zero to three substituents independently selectedfrom —OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃alkyl), —NR_(x)R_(x), phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl),and —CH₂CH₂(pyrrolidinyl); each R_(b) is independently —CH₃ or —CF₃; andeach R_(x) is independently H or —CH₃. Included in this embodiment arecompounds in which R₃ is —CH₂C(O)NH(cyclobutyl),—CH₂C(O)NH(cyclopropyl), —CH₂C(O)NH(methyloxetanyl),—CH₂C(O)N(CH₃)(cyclopropyl), oxetanyl, tetrahydropyranyl,dioxotetrahydrothiopyranyl, —CH₂(oxazolyl), —CH₂(pyrazolyl),—CH₂(tetrazolyl), —CH₂(triazolyl), —CH₂(methyltriazolyl),—CH₂C(O)(2-oxa-6-azaspiro[3.3]heptanyl), —CH₂C(O)(azetidinyl),—CH₂C(O)(dioxidothiadiazinanyl), —CH₂C(O)(dioxidothiomorpholinyl),—CH₂C(O)(morpholinyl), —CH₂C(O)(methoxyethylpiperazinyl),—CH₂C(O)(piperidinyl), —CH₂C(O)(hydroxypiperidinyl),—CH₂C(O)(pyrrolidinyl), —CH₂C(O)(hydroxypyrrolidinyl),—C(O)(azetidinyl), —C(O)(methylcyclopropyl), —C(O)(methyloxetanyl), or—C(O)CH₂(morpholinyl). Also included are compounds in which m is zeroand n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is H, C₁₋₆ alkyl, C₁₋₃ cyanoalkyl, C₁₋₄ hydroxyalkyl,—(CR_(x)R_(x))₁₋₄O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₄O(CR_(x)R_(x))₁₋₃O(C₁₋₃alkyl), —CH₂CH(OH)CH₂O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),—(CH₂)₁₋₃C(O)OC(CH₃)₃, —(CR_(x)R_(x))₀₋₃NR_(x)R_(y),—(CR_(x)R_(x))₀₋₃NR_(x)(C₁₋₄ hydroxyalkyl), —CH₂CH(OH)CH₂NR_(x)R_(y),—C(O)(C₁₋₆ alkyl), —C(O)(C₁₋₃ hydroxyalkyl), —C(O)(C₁₋₃ fluoroalkyl),—C(O)(C₁₋₃ chloroalkyl), —C(O)(C₁₋₃ cyanoalkyl),—(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(CH₂)₁₋₂O(C₁₋₂ alkyl),—C(O)(CR_(x)R_(x))₀₋₂O(CR_(x)R_(x))₁₋₂O(C₁₋₃ alkyl),—C(O)CR_(x)R_(x)S(O)₂(C₁₋₃ alkyl), —C(O)CR_(x)R_(x)NR_(x)S(O)₂(C₁₋₃alkyl), —C(O)CR_(x)R_(x)OC(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₃NR_(y)R_(y), —C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₃cyanoalkyl), —C(O)(CR_(x)R_(x))₀₋₂NR_(y)(C₁₋₆ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₃ fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(C₁₋₅ hydroxy-fluoroalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂O(C₁₋₃ hydroxyalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₂ alkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)((CR_(x)R_(x))₁₋₂O(C₁₋₂ alkyl)),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)R_(x),—C(O)CR_(x)(NH₂)(CR_(x)R_(x))₁₋₄NR_(x)C(O)N_(x)C(O)NR_(x)R_(x),—C(O)(CR_(x)R_(x))₀₋₃NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ alkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₀₋₁C(O)(C₁₋₃ cyanoalkyl),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),—C(O)(CR_(x)R_(x))₀₋₁NR_(x)(CHR_(y)(CH₂OH)),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃fluoroalkyl), —(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₄ hydroxyalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(y)(C₁₋₃ cyanoalkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)(CH₂)₁₋₂O(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₂C(O)NR_(x)CH(C₁₋₄ alkyl)(C₁₋₃ hydroxyalkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂C(O)NR_(x)R_(x),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂S(O)₂₀OH,—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₂NR_(x)C(O)(C₁₋₃ alkyl),—(CH₂)₁₋₂C(O)NR_(x)(CH₂)₁₋₃NR_(x)R_(x),—(CH₂)₁₋₂C(O)N(CH₂CH₃)(CH₂)₁₋₃NR_(x)R_(x), —(CH₂)₁₋₂S(O)₂(C₁₋₄ alkyl),—(CH₂)₀₋₂S(O)₂(C₁₋₃ fluoroalkyl), —(CH₂)₁₋₂S(O)₂NR_(x)R_(x),—C(O)C(O)OH, —C(O)C(O)NR_(y)R_(y), or—C(O)C(O)NR_(y)(CR_(x)R_(x))₁₋₂NR_(y)R_(y); and R₁, R₂, R₄, R₅, R_(x),R_(y), m, n, and p are defined in the first aspect. Included in thisembodiment are compounds in which R₃ is H, —CH(CH₃)₂, —CH(CH₃)₂,—CH₂CH(CH₃)₂, —CH₂CN, —CH₂CH₂CN, —CH₂CH₂CH₂CN, —CH₂C(CH₃)₂OH, —C(O)CH₃,—C(O)CH(CH₂CH₃)₂, —C(O)CH₂OCH₃, —C(O)CH₂CH₂OCH₃, —C(O)CH₂CH(CH₃)OH,—C(O)CH₂CN, —C(O)CH₂CH₂CN, —C(O)CH(CH₃)NH(CH₃), —C(O)CH₂NH(CH₃),—C(O)CH₂N(CH₃)₂, —C(O)CH₂NHCH₂CH₂CH₃, —C(O)CH₂NHCH(CH₃)₂,—C(O)CH₂NHC(CH₃)₃, —C(O)CH₂N(CH₃)CH(CH₃)₂, —C(O)CH₂NHCH₂CH₂OCH₃,—CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)CH₂CH₃, —CH₂C(O)NHCH₂CH₂CH₃,—CH₂C(O)NH(CH(CH₃)₂), —CH₂C(O)N(CH₃)₂, —CH₂C(O)N(CH₂CH₃)₂,—CH₂CH₂S(O)₂CH₃, or —CH₂CH₂S(O)₂NH₂. Also included are compounds inwhich m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₃ is H, —CH(CH₃)₂, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂CN, —CH₂CH₂CN,—CH₂CH₂CH₂CN, —CH₂C(CH₃)₂OH, —C(O)CH₃, —C(O)CH(CH₂CH₃)₂, —C(O)CH₂OCH₃,—C(O)CH₂CH₂OCH₃, —C(O)CH₂CH(CH₃)OH, —C(O)CH₂CN, —C(O)CH₂CH₂CN,—C(O)CH(CH₃)NH(CH₃), —C(O)CH₂NH(CH₃), —C(O)CH₂N(CH₃)₂,—C(O)CH₂NHCH₂CH₂CH₃, —C(O)CH₂NHCH(CH₃)₂, —C(O)CH₂NHC(CH₃)₃,—C(O)CH₂N(CH₃)CH(CH₃)₂, —C(O)CH₂NHCH₂CH₂OCH₃, —CH₂C(O)NH₂,—CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)CH₂CH₃, —CH₂C(O)NHCH₂CH₂CH₃,—CH₂C(O)NH(CH(CH₃)₂), —CH₂C(O)N(CH₃)₂, —CH₂C(O)N(CH₂CH₃)₂,—CH₂CH₂S(O)₂CH₃, —CH₂CH₂S(O)₂NH₂, —CH₂C(O)NH(cyclobutyl),—CH₂C(O)NH(cyclopropyl), —CH₂C(O)NH(methyloxetanyl),—CH₂C(O)N(CH₃)(cyclopropyl), oxetanyl, tetrahydropyranyl,dioxotetrahydrothiopyranyl, —CH₂(oxazolyl), —CH₂(pyrazolyl),—CH₂(tetrazolyl), —CH₂(triazolyl), —CH₂(methyltriazolyl),—CH₂C(O)(2-oxa-6-azaspiro[3.3]heptanyl), —CH₂C(O)(azetidinyl),—CH₂C(O)(dioxidothiadiazinanyl), —CH₂C(O)(dioxidothiomorpholinyl),—CH₂C(O)(morpholinyl), —CH₂C(O)(methoxyethylpiperazinyl),—CH₂C(O)(piperidinyl), —CH₂C(O)(hydroxypiperidinyl),—CH₂C(O)(pyrrolidinyl), —CH₂C(O)(hydroxypyrrolidinyl),—C(O)(azetidinyl), —C(O)(methylcyclopropyl), —C(O)(methyloxetanyl), or—C(O)CH₂(morpholinyl); and R₁, R₂, R₄, R₅, m, n, and p are defined inthe first aspect. Included in this embodiment are compounds in whicheach R₂ is independently F, —CN, —OH, C₁₋₂ alkyl, or —(CH₂)₀₋₁O(C₁₋₂alkyl); p is zero, 1 or 2. Included in this embodiment are compounds inwhich each R₂ is independently —CH₃, —OCH₃, or —CH₂OCH₃. Also includedare compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein m is zero, 1, or 2; and R₁, R₂, R₃, R₄, R₅, n, and p are definedin the first aspect. Included in this embodiment are compounds in whichm is zero or 1. Also included in this embodiment are compounds in whichm is zero. Also included are compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein n is zero or 1; and R₁, R₂, R₃, R₄, R₅, m, and p are defined inthe first aspect. Included in this embodiment are compounds in which nis zero. Also included are compounds in which m is zero. Also includedare compounds in which m is zero and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein m is zero, 1, or 2; n is zero or 1; and p is zero, 1, or 2; andR₁, R₂, R₃, R₄, and R₅ are defined in the first aspect. Included in thisembodiment are compounds in which m is zero or 1; n is zero; and p iszero, 1, or 2. Also included are compounds in which m is zero; n iszero; and p is zero, 1, or 2.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-1):

and R₁, R₃, R₄, R₅, m, and n are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which R₁ is—CHCH₃ or —CH(CH₃)₂. Included in this embodiment are compounds in whichR₃ is H, —CH₃, —CH(CH₃)₂, —CH₂CHF₂, —CH₂CH₂OH, —CH₂C(O)NH₂,—CH₂C(O)NH(CH₃), —CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)₂, —CH₂C(CH₃)₂OH,—C(O)CH₂S(O)₂CH₃, —C(O)CH₂NH(CH₃), —C(O)CH₂N(CH₃)₂, —C(O)CH₂CH(CH₃)OH,or -L₁-A; L₁ is —CH₂—, —C(O)—, or —C(O)CH₂CH(CH₃)—; and A is isoxazolyl,oxazolyl, oxetanyl, pyrazolyl, pyrimidinyl, pyrrolidinonyl,tetrahydrofuranyl, tetrahydropyranyl, thiazolyl, or triazolyl, eachsubstituted with -L₂-R_(a) and zero to 2 R_(b); L₂ is a bond; R_(a) isH, C₁₋₃ alkyl, —OCH₃, or —CH₂(cyclopropyl); and each R_(b) is —CH₃. Alsoincluded in this embodiment are compounds in which R₁ is —CH(CH₃)₂; m iszero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(1);1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(47);1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(51); (S)-1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(53);6-(3-ethyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(121);2-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (164);2-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(240);1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(241); 2-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(242);6-(3-isopropyl-5-(1-methylpiperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(350);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(351);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(352); 6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (353);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(354);6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(355);2-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-ol(356);6-(3-isopropyl-5-(1-(oxetan-3-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(358);6-(3-isopropyl-5-(1-((2-methoxypyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (359);2-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (360);3-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-5-methylisoxazole(361);4-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-2-isopropylthiazole(362);6-(3-isopropyl-5-(1-((1-propyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (363);6-(5-(1-((3,5-dimethyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(364);6-(5-(1-((1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(365);6-(5-(1-((1-(cyclopropylmethyl)-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(366);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(367);6-(3-isopropyl-5-(1-((5-methoxy-1,3-dimethyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(368);5-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-2,4-dimethylthiazole(369); 4-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-3,5-dimethylisoxazole(370);6-(5-(1-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(371);4-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-2,5-dimethyloxazole(372);6-(5-(1-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(373);2-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)thiazole(374); 6-(3-isopropyl-5-(1-((1-isopropyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(375);6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (376);5-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)thiazole (377);4-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-2-methyloxazole(378);6-(5-(1-((1H-pyrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (379);6-(3-isopropyl-5-(1-((3-methyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(380);6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(381);6-(5-(1-((1-ethyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(382);2-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-5-methylthiazole (383);4-((4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)oxazole(384);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(536);4-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one(601);1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylsulfonyl)ethan-1-one(619); or 1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(oxetan-3-yl)butan-1-one(713).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-2):

and R₁, R₃, R₄, R₅, m, and n are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which R₁ is—CH(CH₃)₂. Included in this embodiment are compounds in which R₃ is H,C₁₋₃ cyanoalkyl, —CH₂C(CH₃)₂OH, —CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)₂,—CH₂C(O)NH(CH₂CH₃), —CH₂C(O)NH(CH(CH₃)₂), —CH₂C(O)N(CH₃)(CH₂CH₃),—CH₂C(O)N(CH₂CH₃)₂, —CH₂C(O)N(CH₃)(CH₂CH₂OH), —CH₂CH₂S(O)₂CH₃,—CH(CH₃)CH₂S(O)₂CH₃, —CH₂CH₂S(O)₂NH₂, —CH₂CH₂S(O)₂NH(CH₃),—CH₂CH₂S(O)₂N(CH₃)₂, —CH₂CH₂NHS(O)₂CH₃, —C(O)CH₂CN, or -L₁-A; L₁ is—CH₂—, —CH₂C(O)—, —CH₂C(O)NH—, or —C(O)CH₂CH₂—; and A is cyclopropyl,dioxotetrahydrothiophenyl, dioxotetrahydrothiopyranyl, isoxazolyl,morpholinyl, oxadiazolyl, oxazolyl, oxetanyl, piperidinyl, pyrazinyl,pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolidinyl, tetrahydropyranyl,thiazolyl, or triazolyl, each substituted with -L₂-R_(a) and zero to 1R_(b); L₂ is a bond; R_(a) is H, —CH₃, —CN, or —OCH₃; and R_(b) is—OCH₃. Also included in this embodiment are compounds in which R₁ is—CH(CH₃)₂; m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (3);3-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-oxopropanenitrile (49);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(180);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile(181);1-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(182);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(183);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylethane-1-sulfonamide(184);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylethane-1-sulfonamide(185);1-((4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)cyclopropane-1-carbonitrile (186);1-((4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)cyclopropane-1-carbonitrile(187);3-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propanenitrile (188);N-(2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethyl)methanesulfonamide(189);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(190);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (191);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (441);6-(3-isopropyl-5-(1-((2-methoxypyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(442);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(443);6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(444);6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(445);2-((4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)oxazole(446);6-(3-isopropyl-5-(1-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(447);6-(5-(1-((1H-pyrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(448);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (449);5-((4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)thiazole(450); 6-(5-(1-((1H-1,2,3-triazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(451);6-(3-isopropyl-5-(1-(pyrimidin-5-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (452);3-((4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)-5-methylisoxazole(453);6-(3-isopropyl-5-(1-(pyrimidin-2-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (454);4-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (455);6-(5-(1-((4,6-dimethoxypyrimidin-2-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(456); 6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(457);2-((4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)-1,3,4-oxadiazole (458);6-(5-(1-((1H-1,2,4-triazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(459);3-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydrothiophene 1,1-dioxide (460);6-(3-isopropyl-5-(1-(pyridazin-3-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine((461);3-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butanenitrile(462);6-(3-isopropyl-5-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(463);6-(3-isopropyl-5-(1-(1-(methylsulfonyl)propan-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(464);6-(3-isopropyl-5-(1-((2-methylpyrimidin-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(465); 6-(3-isopropyl-5-(1-((5-methylpyrazin-2-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(466);6-(3-isopropyl-5-(1-(pyrazin-2-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (467);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one(802);N-isopropyl-2-(4-(3-isopropyl-2-(7-methyl-1-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(803);N-ethyl-2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (804);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(piperidin-1-yl)ethan-1-one(805);N-cyclopropyl-2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (806);N-ethyl-2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(807);N,N-diethyl-2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(808);2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one (809);N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(810); or1-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-morpholinopropan-1-one (885).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-3):

R₂ is —CH₃ or —CD₃; and R₁, R₃, R₄, R₅, m, and n are defined in thefirst aspect or the second aspect. Included in this embodiment arecompounds in which R₁ is —CHCH₃, —CH(CH₃)₂, or —CH₂CHF₂. Included inthis embodiment are compounds in which R₃ is H, C₃₋₅ alkyl, C₂₋₃fluoroalkyl, C₂₋₅ hydroxyalkyl, C₁₋₃ cyanoalkyl, —CH₂C(CH₃)₂OH,—CH₂CH₂OCH₃, —CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —CH₂C(O)NH(CH₂CH₂CH₃),—CH₂C(O)NH(CH(CH₃)₂), —CH₂C(O)N(CH₃)₂, —CH₂C(O)N(CH₃)CH₂CH₃,—CH₂C(O)N(CH₂CH₃)₂, —CH(CN)C(O)N(CH₃)₂, —CH₂C(O)N(CH₃)(CH₂CH₂OH),—CH₂C(O)N(CH₂CH₃)(CH₂CH₂OH), —CH₂C(O)N(CH₂CH₂CH₃)(CH₂CH₂OH),—CH₂C(O)N(CH₃)(CH₂CH₂CH₂OH), —CH₂C(O)N(CH₃)(CH₂C(CH₃)₂OH),—CH₂C(O)N(CH₂CH₂OH)(CH₂CH(CH₃)CH₂CH₃), —CH₂C(O)NH(CH₂CH₂SCH₃),—CH₂CH₂S(O)₂CH₃, —CH₂CH₂CH₂S(O)₂CH₃, —CH(CH₃)CH₂S(O)₂CH₃,—CH(CH₃)CH₂S(O)₂(CH₂CH₂CH₂CH₃), —CH₂CH₂S(O)₂NH₂, —CH₂CH₂S(O)₂NH(CH₃),—CH₂CH₂S(O)₂N(CH₃)₂, —CH(CH₃)CH₂S(O)₂N(CH₂CH₃)₂, —CH₂CH₂NHS(O)₂CH₃,—C═N(NH₂), —C(O)CH₃, —C(O)CH(CH₂CH₃)₂, —C(O)CH₂CH₂CN, —C(O)CH₂CH(CH₃)OH,—C(O)CH₂OCH₃, —C(O)CH₂CH₂OCH₃, —C(O)CH₂NH(CH₃), —C(O)CH₂NH(CH₂CH₂CH₃),—C(O)CH₂NHCH(CH₃)₂, —C(O)CH₂NHC(CH₃)₃, —C(O)CH₂N(CH₃)₂,—C(O)CH(CH₃)NH(CH₃), —C(O)CH₂N(CH₃)CH(CH₃)₂, —C(O)CH₂N(CH₃)(CH₂CH₂OH),—C(O)CH₂NH(CH₂CH₂OCH₃), —C(O)CH₂S(O)₂CH₃, —C(O)CH₂CH₂S(O)₂CH₃,—C(O)CH₂NHS(O)₂CH₃, or -L₁-A; L₁ is —CH₂—, —CH₂C(O)—,—CH₂C(O)N(CH₂CH₂OH)—, —CH₂C(O)N(CH₃)—, —CH₂C(O)N(CH₃)—,—CH₂C(O)N(CH₃)CH₂CH₂—, —CH₂C(O)NH—, —CH₂CH₂S(O)₂—, —C(O)—, —C(O)CH₂—,—C(O)CH₂CH₂—, —C(O)CH₂CH₂N(CH₂CH₂OH)—, —C(O)CH₂N(CH₂CH₂OH)—,—C(O)CH₂NH—, —CH(CH₃)—, or —CH(CH₃)CH₂S(O)₂—; and A is2-oxa-6-azaspiro[3.3]heptanyl, azetidinyl, C₃₋₆ cycloalkyl,dioxidothiadiazinanyl, dioxidothiazolidinyl, dioxidothiomorpholinyl,dioxotetrahydrothiophenyl, dioxotetrahydrothiopyranyl,dioxothiomorpholinyl, imidazolyl, isoxazolyl, morpholinyl,oxa-azaspiro[3.3]heptanyl, oxadiazolyl, oxazolyl, oxetanyl, phenyl,piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridazinyl,pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, tetrahydrofuranyl,tetrahydropyranyl, tetrahydrothiopyranyl, tetrazolyl, thiadiazolyl,thiazolyl, or triazolyl, each substituted with -L₂-R_(a) and zero to 2R_(b); L₂ is a bond; R_(a) is H, F, —CH₃, —CN, —OH, —OCH₃, —CH₂OH,—CH₂CH₂OH, —CH₂CH₂OCH₃, —C(O)CH₃, —C(O)OCH₂CH₃, —C(O)OC(CH₃)₃,—NHC(O)OC(CH₃)₃, —S(O)₂CH₃, cyclopropyl, or pyrazinyl; and each R_(b) isindependently F, —OH, —CH₃, or —OCH₃. Also included in this embodimentare compounds in which R₁ is —CH(CH₃)₂; m is zero, and n is zero.Additionally, included in this embodiment are compounds in which R₂ is—CH₃.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine hydrochloride (2);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(7);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile(8);3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propanenitrile(9);6-(5-(1-butylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(10);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(11);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(12);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (26);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (27);6-(3-isopropyl-5-(1-propylpiperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(28);6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(29);6-(5-(1-((1H-pyrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(30);4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)oxazole(31);6-(5-(1-((1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(32);6-(5-(1-((4H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(33);6-(5-(1-((1H-tetrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(34);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(35);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(36);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (37);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(46);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(48);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (50);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methoxyethan-1-one(52);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-4-oxobutanenitrile(54);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylcyclopropyl)methanone(55);(S)-azetidin-2-yl(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone (56);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(57);(S)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)propan-1-one (58);(R)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)propan-1-one(59);(S)-3-hydroxy-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-one(60);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methoxypropan-1-one (61);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(3-methyloxetan-3-yl)methanone(64);2-ethyl-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-one (65);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-morpholinoethan-1-one(68);2-(tert-butylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (69);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(isopropylamino)ethan-1-one(70);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-((2-methoxyethyl)amino)ethan-1-one (71);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(propylamino)ethan-1-one(72);2-(isopropyl(methyl)amino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(73);1-(1,1-dioxidothiomorpholino)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(74);N-cyclopropyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (75);N-ethyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (76);(S)-1-(3-hydroxypiperidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (77);N-cyclobutyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(78);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethan-1-one(79);N,N-diethyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(80);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-propylacetamide(81);(R)-1-(3-hydroxypiperidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(82);(S)-1-(3-hydroxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(83);(R)-1-(3-hydroxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (84);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(4-(2-methoxyethyl)piperazin-1-yl)ethan-1-one(85);1-(azetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(86);N-isopropyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (87);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one(88);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(piperidin-1-yl)ethan-1-one (89);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one(90);1-(1,1-dioxidothiomorpholino)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (91);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(3-methyloxetan-3-yl)acetamide(92);N-cyclopropyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(93);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-(trideuteromethyl)-[1,2,4]triazolo[1,5-a]pyridine(117);6-(3-ethyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (158);6-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(161);6-(5-(1-isopentylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(165); 6-(3-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(166);4-((2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethyl)sulfonyl)morpholine (167);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(168);2-cyano-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (169);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propanenitrile (170);1-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)cyclopropane-1-carbonitrile (171-172);6-(3-isopropyl-5-(1-(2-(phenylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(173);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylethane-1-sulfonamide(174);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylethane-1-sulfonamide(175);N-(2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethyl)methanesulfonamide (176);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(177);6-(3-isopropyl-5-(1-(3-(methylsulfonyl)propyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (178);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)-[1,4′-bipiperidin]-1′-yl)ethan-1-one(179); 4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one(243);2-(4-(3-ethyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(337);2-(4-(3-ethyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(338); 6-(3-ethyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(339);2-(4-(3-ethyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(340);6-(3-ethyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(341);1-(4-(3-ethyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(342);2-(4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(343);2-(4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(344);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trideuteromethyl)-[1,2,4]triazolo[1,5-a]pyridine (357);6-(5-(1-(2,2-difluoroethyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(385);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(386);6-(3-isopropyl-5-(1-((2-methoxypyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(387); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-ol (388);6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(389);3-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)-1,2,4-oxadiazole (390);3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-ol(391);6-(3-isopropyl-5-(1-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (392); 6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(393);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(394);3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydrothiophene1,1-dioxide (395);6-(3-isopropyl-5-(1-(pyrimidin-2-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(396);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-ol (397);6-(5-(1-(2,6-difluorobenzyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(398); 6-(5-(1-((3,5-dimethyl-112-pyrazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(399);(3,5-difluoro-4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)phenyl)methanol(400);3,5-difluoro-4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triaizol[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)benzonitrile(401);6-(3-isopropyl-5-(1-(pyrimidin-5-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(402);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclohexan-1-ol(403);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(404);6-(5-(1-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(405);4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)thiazole(406);4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)-5-methylthiazole (407);2-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)thiazole (408);6-(3-isopropyl-5-(1-((3-methyl-1H-pyrazol-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(409);6-(5-(1-((1,5-dimethyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(410);4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)-1,2,3-thiadiazole(411);6-(3-isopropyl-5-(1-(pyridazin-3-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(412); (2-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)pyrimidin-5-yl)methanol(413);6-(3-isopropyl-5-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(414); 6-(3-isopropyl-5-(1-((2-methylpyrimidin-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(415);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-methylcyclopentane-1-carbonitrile(416-417);6-(3-isopropyl-5-(1-(1-(6-methylpyridazin-3-yl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (418);6-(3-isopropyl-5-(1-(1-(1-methyl-1H-pyrazol-4-yl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(419);6-(5-(1-(1-(1H-pyrazol-5-yl)ethyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(420);6-(3-isopropyl-5-(1-(1-(pyrimidin-2-yl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (421);6-(3-isopropyl-5-(1-(1-(methylsulfonyl)propan-2-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(422);3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butanenitrile(423);6-(3-isopropyl-5-(1-((5-methylpyrazin-2-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (424);6-(3-isopropyl-5-(1-(tetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(425);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(1H-tetrazol-5-yl)ethan-1-one(426);N,N-diethyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propane-1-sulfonamide(427);6-(5-(1-(1-(butylsulfonyl)propan-2-yl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (428);6-(3-isopropyl-5-(1-(pyrazin-2-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(429);4-((2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propyl)sulfonyl)morpholine(430);6-(3-isopropyl-5-(1-(1-(piperidin-1-ylsulfonyl)propan-2-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (431);3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)pentane-1,5-diol(432);6-(3-isopropyl-5-(1-((2-methyl-2H-tetrazol-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(433);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(434);3-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)-5-methylisoxazole(435);5-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)thiazole(436);6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(437);6-(5-(1-((4,6-dimethoxypyrimidin-2-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(438);5-cyclopropyl-2-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)oxazole(439);2-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)oxazole (440);6-(3-isopropyl-5-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(537); tert-butyl(3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclobutyl)carbamate(538); ethyl3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclobutane-1-carboxylate (539);6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(540-541);6-(3-ethyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(596);6-(3-(2,2-difluoroethyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(597);2-(4,4-difluoropiperidin-1-yl)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(602);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(pyrazin-2-yl)ethan-1-one(603);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-(pyrazin-2-yl)cyclopropyl)methanone(604);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(2-methyl-2H-tetrazol-5-yl)ethan-1-one(605);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylsulfonyl)ethan-1-one(606);N-(2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)methanesulfonamide (607);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-(methylsulfonyl)propan-1-one(608);6-(3-isopropyl-5-(1-((2-methyl-1H-imidazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(620); (4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(2,2,3,3-tetramethylcyclopropyl)methanone(621);((2S,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(622);((2S,3R)-3-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(623);((2S,4S)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(624);((2R,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(625);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)((2S,4R)-4-methoxypyrrolidin-2-yl)methanone(626);((2S,4R)-4-fluoropyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazol[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(627);1-((2S,4R)-4-hydroxy-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)pyrrolidin-1-yl)ethan-1-one(628);2-(dimethylamino)-1-(4-(3-ethyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(703);1-(4-(3-ethyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(704); (R)-1-(4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(705);1-(4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(706);(S)-1-(4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(707);1-(4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(712);2-((2-hydroxyethyl)(methyl)amino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (714);2-(cyclopropyl(2-hydroxyethyl)amino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(715);2-(3,3-difluoropyrrolidin-1-yl)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(716);2-(1,1-dioxidothiomorpholino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(717);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-((1-methylcyclopropyl)amino)ethan-1-one (768);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(piperidin-1-yl)ethan-1-one (769);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(pyrrolidin-1-yl)ethan-1-one(770);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethan-1-one (771);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(4-(2-methoxyethyl)piperazin-1-yl)ethan-1-one(772);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(4-methoxypiperidin-1-yl)ethan-1-one (773);(S)-2-(3-hydroxypyrrolidin-1-yl)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (774);(S)-2-(3-hydroxypiperidin-1-yl)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(775);(R)-2-(3-hydroxypyrrolidin-1-yl)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(776);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(3-(methylsulfonyl)azetidin-1-yl)ethan-1-one (782);1-(1,1-dioxidothiazolidin-3-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(783-784);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(2-(methylthio)ethyl)acetamide (785);1-((2R,4R)-2-(hydroxymethyl)-4-methoxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(786);N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(787);N-ethyl-N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(788);N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-propylacetamide(789);(R)-1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(790);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide(791);N-(3-hydroxypropyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(792);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide(793);N-(2-(1-hydroxycyclopentyl)ethyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(794); (R)-1-(3-(hydroxymethyl)morpholino)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(795);N-(2-hydroxy-2-methylpropyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazol[5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(796);(S)-1-(3-(hydroxymethyl)morpholino)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (797);(S)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide(798);1-((2R,4R)-2-(hydroxymethyl)-4-methylpyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (799);N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(2-methylbutyl)acetamide(800);N-cyclopropyl-N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(801);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-morpholinopropan-1-one(882);3-(cyclopropyl(2-hydroxyethyl)(methyl)-14-azaneyl)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one(883);3-(1,1-dioxidothiomorpholino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one(884); or4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboximidamide(994).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-4):

and R₁, R₃, R₄, R₅, m, and n are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which R₁ is—CHCH₃, —CH(CH₃)₂, or —CH₂CHF₂. Included in this embodiment arecompounds in which R₃ is H, —CH₂CH(CH₃)₂, —CH₂CN, —CH₂C(CH₃)₂OH,—CH₂CH₂OCH₃, —CH₂CH₂NH(CH₃), —CH₂CH₂S(O)₂CH₃, —CH(CH₃)CH₂S(O)₂CH₃,—CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —CH₂C(O)N(CH₃)₂, —CH₂C(O)NH(CH₂C(CH₃)₂OH),—CH₂C(O)N(CH₃)(CH₂CH₃), —C(O)CH₂S(O)₂CH₃, —C(O)CH₂OCH₃, —C(O)CH₂NH(CH₃),—C(O)CH₂NH(CH₂CH₂OCH₃), —C(O)CH₂N(CH₃)₂, —C(O)CH₂CH₂OCH₃,—C(O)CH₂CH₂N(CH₃)₂, —C(O)CH₂CH₂CH₂S(O)₂NH₂, —C(O)CH₂C(CH₃)₂OH, or -L₁-A;L₁ is —CH₂—, —C(O)—, —C(O)CH₂—, —C(O)CH₂CH₂—, —C(O)CH₂NH—, —CH₂C(O)—, or—CH₂C(O)NH—; and A is azetidinyl, cyclobutyl, dioxanyl,dioxotetrahydrothiopyranyl, dioxothiomorpholinyl, morpholinyl, oxetanyl,piperazinonyl, pyrrolidinonyl, pyrrolidinyl, tetrahydrofuranyl, ortetrahydropyranyl, each substituted with -L₂-R_(a) and zero to 1 R_(b);L₂ is a bond; R_(a) is H, F, C₁₋₂ alkyl, —CN, —OH, —OCH₃, —C(O)CH₃, or—C(O)OC(CH₃)₃; and R_(b) is F or —CH₃. Also included in this embodimentare compounds in which R₁ is —CH(CH₃)₂; m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(5);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile(21);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(22);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(23);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(24);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(25);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(44);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (45);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (62);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methoxyethan-1-one(63);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(67);6-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (156);6-(3-ethyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (157);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (263);6-(3-isopropyl-5-(1-(1-(methylsulfonyl)propan-2-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (264);6-(3-isopropyl-5-(1-(1-(methylsulfonyl)propan-2-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (265); 6-(3-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(266);2-(4-(3-(2,2-difluoroethyl)-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(329); 2-(4-(3-(2,2-difluoroethyl)-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(330); 2-(4-(3-ethyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(331);6-(3-ethyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (332);2-(4-(3-ethyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (333);1-(4-(3-ethyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(334);2-(4-(3-ethyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(335); 6-(3-ethyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine(336);1-(4-(3-(2,2-difluoroethyl)-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(349);4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (561);6-(5-(1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(562-564); (R)-3-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl) methyl)morpholine(565);6-(3-isopropyl-5-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo [1,5-a]pyridine (566);3-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)cyclobutane-1-carbonitrile(567);6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (568-569);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylethan-1-amine(570);6-(3-(2,2-difluoroethyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (598);6-(3-ethyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (600); (4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(tetrahydrofuran-2-yl)methanone(663);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methoxypropan-1-one(664); 4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl) piperidin-1-yl)-4-oxobutane-1-sulfonamide(665);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(tetrahydro-2H-pyran-4-yl)ethan-1-one (666);3-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one(667);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylsulfonyl)ethan-1-one (668);3-hydroxy-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methylbutan-1-one(669);(S)-1-(2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)pyrrolidin-1-yl)ethan-1-one (670);1-(3-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-oxopropyl)pyrrolidin-2-one (671);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpyrrolidin-3-yl)methanone (672);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-morpholinoethan-1-one(673);((2S,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(674);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)((2S,4R)-4-methoxypyrrolidin-2-yl)methanone(675);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpyrrolidin-3-yl)methanone (676);4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one(677); 4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one(678);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpyrrolidin-3-yl)methanone(679);2-(dimethylamino)-1-(4-(3-ethyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(701);1-(4-(3-ethyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(702);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-((2-methoxyethyl)amino)ethan-1-one(780); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-((3-methyloxetan-3-yl)amino)ethan-1-one(781);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(3-methyloxetan-3-yl) acetamide (854); tert-butyl3-(2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamido)azetidine-1-carboxylate (855);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(4-methyltetrahydro-2H-pyran-4-yl)acetamide(856);N-(2-hydroxy-2-methylpropyl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (857);1-(1,1-dioxidothiomorpholino)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(858);N-ethyl-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(859);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(1-methylcyclobutyl)acetamide(860);N-((3-ethyloxetan-3-yl)methyl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (861);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-((3-methyloxetan-3-yl)methyl)acetamide(862);(R)-1-(3-hydroxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (863);1-(3-fluoroazetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (864);1-(3,3-difluoroazetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (865);4-(2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetyl)piperazin-2-one (866);1-(3-hydroxyazetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(867);(R)-1-(3-fluoropyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (868);1-((2S,6R)-2,6-dimethylmorpholino)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (869);1-(azetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(870); (R)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(3-methylmorpholino)ethan-1-one(871);1-(3,3-difluoropyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(872);1-(2,5-dimethylpyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (873);(S)-1-(3-hydroxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (874);(S)-1-(3-fluoropyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(875);2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (991);6-(4-fluoro-5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(992); or 6-(5-(1-(2,2-dimethyl-1,3-dioxan-5-yl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (993).

One embodiment provides a compound of Formula (I-4) or a salt thereof,wherein R₁ is —CH(CH₃)₂; m is zero; n is zero, and R₃ is defined in thefirst aspect or the second aspect. Compounds of this embodiment have thestructure of Formula (I-4a)

Included in this embodiment are compounds in which R₃ is—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y) wherein each R_(x) is independently Hor —CH₃; and each R_(x) is independently H or —CH₃. Also included inthis embodiment are compounds in which R₃ is —CH₂C(O)NH₂,—CH₂C(O)NH(CH₃), or —CH₂C(O)N(CH₃)₂.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is:

Included in this embodiment is2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(25). Also included in this embodiment is one or more salts of2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-5):

and R₁, R₃, R₄, R₅, m, and n are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which R₁ is—CH(CH₃)₂. Included in this embodiment are compounds in which R₃ is H,—CH₂CN, —CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —CH₂C(O)NH(CH₂CH₃),—CH₂C(O)NH(CH₂CH₂CN), —CH₂C(O)NH(CH₂CH₂CF₃), —CH₂C(O)NH(CH(CH₃)₂),—CH₂C(O)N(CH₃)CH₂CH₂OCH₃, —CH₂C(O)N(CH₃)CH₂CH₂CN,—CH₂C(O)N(CH₃)CH₂CH₂CH₂OH, —CH₂CH₂S(O)₂NH₂, —CH₂CH₂S(O)₂CH₃,—CH₂C(O)NHCH(CH₂CH₂OH)(cyclopropyl), or -L₁-A; L₁ is —CH₂—, —CH₂CH₂—,—CH₂C(O)—, —CH₂C(O)N(CH₃)—, or —CH₂C(O)N(CH₃)CH₂CH₂—; A is azetidinyl,dioxidothiadiazinanyl, dioxoisothiazolidinyl, dioxothiomorpholinyl,morpholinyl, oxetanyl, piperidinyl, pyrazolyl, pyrimidinyl,pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, or triazolyl, eachsubstituted with -L₂-R_(a) and zero to 1 R_(b); L₂ is a bond; R_(a) isH, F, —CH₃, —CN, —CH₂OH, or —S(O)₂CH₃; and R_(b) is F, —CH₃, —CF₃, or—OCH₃. Also included in this embodiment are compounds in which R₁ is—CH(CH₃)₂; m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine(6);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(198);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (199);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine (200);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile(201);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(202);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(203);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine(470);6-(3-isopropyl-5-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine (471);6-(3-isopropyl-5-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine(472);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine (473);2-(2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethyl)isothiazolidine1,1-dioxide (474);N-(2-cyanoethyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (811);(S)-1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(812);1-(1,1-dioxido-1,2,4-thiadiazinan-4-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(813);N-(3-hydroxypropyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(814);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide(815);N-ethyl-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(816);N,N-diethyl-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(817);N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(818);N-ethyl-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(819);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(2-methoxyethyl)-N-methylacetamide(820);N-isopropyl-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(821);1-((2R,4R)-2-(hydroxymethyl)-4-methoxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(822);(S)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide(823);1-((2R,4R)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(824);N-ethyl-N-(2-hydroxyethyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(825);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(3-(methylsulfonyl)azetidin-1-yl)ethan-1-one(826);1-(1,1-dioxidothiomorpholino)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(827);N-(2-hydroxy-2-methylpropyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(828);(R)-1-(3-(hydroxymethyl)morpholino)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(829);1-(4,4-difluoropiperidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(830);1-(3,3-dimethylazetidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (831);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(3,3,3-trifluoropropyl)acetamide(832);1-(3,3-difluoropyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (833);N-(1-cyclopropyl-3-hydroxypropyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(834);(R)-1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (835);N-(2-(1H-pyrazol-4-yl)ethyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(836);1-((2R,4R)-2-(hydroxymethyl)-4-methylpyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (837);1-(2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetyl)azetidine-3-carbonitrile (838);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide(839);1-(3,3-difluoroazetidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (840);1-((2S,4S)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(841); orN-(2-cyanoethyl)-2-(4-(3-isopropyl-2-(8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(842).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-6):

and R₁, R₃, R₄, R₅, m, and n are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which R₁ is—CH(CH₃)₂ or —CH₂CHF₂. Included in this embodiment are compounds inwhich R₃ is H, C₁₋₅ alkyl, C₁₋₂ cyanoalkyl, —CH₂CH₂CF₃, —CH₂C(CH₃)₂OH,—CH₂CH₃, —CH₂CH₂OCH₃, —CH₂N(CH₃)₂, —CH₂C(O)NH₂, —CH₂C(O)NH(CH₃),—CH₂C(O)N(CH₃)₂, —CH₂C(O)N(CH₃)(CH₂CH₂OH), —CH₂CH₂S(O)₂CH₃,—CH₂CH₂S(O)₂NH₂, —CH₂CH₂S(O)₂N(CH₃)₂, —CH₂CH₂NHS(O)₂CH₃,—CH₂CH₂N(CH₃)S(O)₂CH₃, —C(O)OCH₂CH₂NH₂, —C(O)OCH₂CH₂N(CH₃)₂,—C(O)OCH₂CH₂N(CH₂CH₃)₂, —C(O)OC(CH₃)₃, —C(O)NHCH₂C(CH₃)₃,—C(O)NH(CH₂CH₂NH₂), —C(O)NH(CH₂CH₂N(CH₃)₂), —C(O)NH(CH₂CH₂CH₂NH₂),—C(O)N(CH₃)CH₂CH₂NH₂, —C(O)CH₂NHCH(CH₃)₂, —C(O)CH₂NHC(CH₃)₃,—C(O)CH₂NH(CH₃), —C(O)CH₂NH(CH₂CN), —C(O)CH₂NH(CH₂CH₃),—C(O)CH₂NH(CH₂CH₂OH), —C(O)CH₂NH(CH₂CH₂OCH₃), —C(O)CH₂NH(CH₂CH₂F),—C(O)CH₂NH(CH₂CH₂CH₃), —C(O)CH₂NH(CH₂CH(CH₃)₂), —C(O)CH₂NH(CH₂CF₃),—C(O)CH₂NH(CH₂C(O)NH₂), —C(O)CH₂N(CH₃)CH₂CH₃, —C(O)CH₂N(CH₃)CH₂CH₂CN,—C(O)CH₂N(CH₃)CH₂CH₂CH₃, —C(O)CH₂N(CH₃)CH₂CH(CH₃)₂,—C(O)CH₂N(CH₃)CH₂C(O)N(CH₃)₂, —C(O)CH₂N(CH₃)CH(CH₃)₂, —C(O)CH₂N(CH₃)₂,—C(O)CH₂N(CH₃)(CH₂CH₂OH), —C(O)CH₂N(CH₃)(CH₂CH₂OCH₃),—C(O)CH₂N(CH₂CH₃)₂, —C(O)CH₂N(CH₂CH₂OCH₃)₂, —C(O)CH₂CH₂NH(CH₃),—C(O)CH₂CH₂NH(CH₂CH₃), —C(O)CH₂CH₂NH(CH₂CH₂OH),—C(O)CH₂CH₂NH(CH₂CH₂OCH₃), —C(O)CH₂CH₂NH(CH₂CH₂F),—C(O)CH₂CH₂NH(CH₂CH₂CH₃), —C(O)CH₂CH₂NH(CH₂C(O)NH₂),—C(O)CH₂CH₂NH(CH₂C(CH₃)₃), —C(O)CH₂CH₂NH(CH(CH₃)₂),—C(O)CH₂CH₂N(CH₃)CH₂CH₂OH, —C(O)CH₂CH₂N(CH₃)CH₂CH₂OCH₃,—C(O)CH₂CH₂N(CH₃)CH₂C(O)N(CH₃)₂, —C(O)CH₂CH₂N(CH₃)(CH₂CH₃),—C(O)CH₂CH₂N(CH₃)(CH₂CH₂CH₃), —C(O)CH₂CH₂N(CH₃)(CH(CH₃)₂), or -L₁-A; L₁is —CH₂—, —CH₂CH₂—, —CH(CN)—, —C(O)—, —C(O)CH₂—, —C(O)CH₂CH₂—,—C(O)CH₂NH—, —C(O)CH₂N(CH₃)—, —C(O)CH₂CH₂NH—, —C(O)CH₂CH₂N(CH₃)—,—C(O)CH₂NHCH₂—, —C(O)CH₂CH₂NHCH₂—, —CH₂C(O)—, —CH₂C(O)NH—, —C(O)NH—,—C(O)NHCH₂—, —C(O)NHCH₂CH₂—, —C(O)O—, —C(O)OCH₂—, or —C(O)OCH₂CH₂—; andA is azepanyl, azetidinyl, cyclobutyl, cyclohexyl, cyclopentyl,cyclopropyl, dioxoisothiazolidinyl, dioxotetrahydrothiopyranyl,dioxothiomorpholinyl, imidazolyl, morpholinyl,octahydropyrrolo[3,4-b]pyridinyl, oxa-azaspiro[3.3]heptan-6-yl,oxetanyl, piperazinonyl, piperazinyl, piperidinonyl, piperidinyl,pyridinyl, pyrimidinyl, pyrrolidinyl, tetrahydrofuranyl,tetrahydropyranyl, triazolonyl, or triazolyl; azetidinyl, cyclobutyl,dioxanyl, dioxotetrahydrothiopyranyl, dioxothiomorpholinyl, morpholinyl,oxetanyl, piperazinonyl, pyrrolidinonyl, pyrrolidinyl,tetrahydrofuranyl, or tetrahydropyranyl, each substituted with -L₂-R_(a)and zero to 1 R_(b); L₂ is a bond; R_(a) is H, F, C₁₋₃ alkyl, C₁₋₂hydroxyalkyl, —CH₂OCH₃, —CH₂CH₂OCH₃, —OH, —OCH₃, —NH₂, —C(O)CH₃,—C(O)CH(CH₂CH₃)₂, —C(O)NH₂, —C(O)N(CH₂CH₃)₂, —C(O)OC(CH₃)₃, —S(O)₂CH₃,or pyridinyl; and R_(b) is F or —CH₃. Also included in this embodimentare compounds in which R₁ is —CH(CH₃)₂; m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (4);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(13);3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propanenitrile(14);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (15);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(16); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(17);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine(18);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(19);4-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (20);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(38); 6-(5-(1-((1H-1,2,3-triazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(39);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(40);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(41);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (42);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(43);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(66);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(110);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(124);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(125);N-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethyl)methanesulfonamide (204); N-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-TH-indol-5-yl)piperidin-1-yl)ethyl)-N-methylmethanesulfonamide(205);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylethane-1-sulfonamide(206);2-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethyl)isothiazolidine1,1-dioxide (475);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(3-methyloxetan-3-yl)acetonitrile (476);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-morpholinoethan-1-one (477);6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(478);6-(5-(1-isopentylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(479);6-(5-(1-ethylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(480);6-(3-isopropyl-5-(1-propylpiperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (481);6-(5-(1-ethylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (482);5-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one(483);6-(3-isopropyl-5-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (484);6-(3-isopropyl-5-(1-methylpiperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(485);6-(3-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(486); tert-butyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(609);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-morpholinopropan-1-one(610);2-(bis(2-methoxyethyl)amino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(718);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(3-hydroxypyrrolidin-1-yl)ethan-1-one (719);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(2,6-dimethylmorpholino)ethan-1-one(720);1-(1-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)piperidin-3-yl)-2-ethylbutan-1-one(721); (S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-TH-indol-5-yl)piperidin-1-yl)-2-(2-(methoxymethyl)pyrrolidin-1-yl)ethan-1-one (722);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(isobutyl(methyl)amino)ethan-1-one (723);1-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)piperidine-4-carboxamide(724); 4-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)piperazin-2-one(725);3-((2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)(methyl)amino)propanenitrile(726);2-(cyclopentylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(727);2-(cyclohexylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(728);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((4-hydroxycyclohexyl)amino)ethan-1-one(729);2-((cyclohexylmethyl)amino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(730);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(((tetrahydrofuran-2-yl)methyl)amino)ethan-1-one(731);2-(tert-butylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(732);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(neopentylamino)ethan-1-one(733);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(propylamino)ethan-1-one(734);(R)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(3-hydroxypyrrolidin-1-yl)ethan-1-one (735);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(3-hydroxypyrrolidin-1-yl)ethan-1-one (736);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(isopropylamino)ethan-1-one(737);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(3-fluoropyrrolidin-1-yl)ethan-1-one (738);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((2-fluoroethyl)amino)ethan-1-one (739);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-ispropyl-1H-indol-5-yl)piperidin-1-yl)-2-(ethylamino)ethan-1-one(740);2-(4,4-difluoropiperidin-1-yl)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(741);2-(cyclopropylamino)-1-(4-(2-(7,8-dimethyl[1,2,4]triazol-[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(742);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((2-methoxyethyl)amino)ethan-1-one(743);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(piperidin-1-yl)ethan-1-one(744); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-TH-indol-5-yl)piperidin-1-yl)-2-(pyrrolidin-1-yl)ethan-1-one (745);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(isobutylamino)ethan-1-one(746); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(3,3-dimethylpiperidin-1-yl)ethan-1-one(747);2-((2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)amino)acetamide(748);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(2-(hydroxymethyl)pyrrolidin-1-yl)ethan-1-one (749);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(4-methoxypiperidin-1-yl)ethan-1-one(750);2-(cyclohexyl(methyl)amino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(751);2-((2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)amino)acetonitrile(752);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (753);2-(azepan-1-yl)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (754);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(4-hydroxypiperidin-1-yl)ethan-1-one(755);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((2-hydroxyethyl)(methyl)amino)ethan-1-one(756);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((2-hydroxyethyl)amino)ethan-1-one(757);2-((cyclopropylmethyl)amino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(758); 2-((2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-oxoethyl)(methyl) amino)-N,N-dimethylacetamide (759);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((2-methoxyethyl)(methyl)amino)ethan-1-one(760);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-((2,2,2-trifluoroethyl)amino)ethan-1-one(761);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methyl(propyl)amino)ethan-1-one (762);2-(diethylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (763);2-(cyclobutylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(764);2-(azetidin-1-yl)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(765);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(ethyl(methyl)amino)ethan-1-one(766);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(isopropyl(methyl)amino)ethan-1-one(767);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one(843);1-(azetidin-1-yl)-2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(844); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-(3-(methylsulfonyl)azetidin-1-yl)ethan-1-one (845);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-(3-methyloxetan-3-yl)acetamide(846);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one(847); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-(2-hydroxyethyl)-N-methylacetamide (848);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethan-1-one(849);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-((4-hydroxycyclohexyl)amino)propan-1-one (886);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(((tetrahydrofuran-2-yl)methyl)amino)propan-1-one(887);(R)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(3-fluoropyrrolidin-1-yl)propan-1-one(888);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-((2-hydroxyethyl)amino)propan-1-one(889);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(propylamino)propan-1-one(890);2-((3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-oxopropyl)amino)acetamide(891);3-((cyclopropylmethyl)amino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one(892);3-(azetidin-1-yl)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl) propan-1-one (893);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(ethyl(methyl)amino)propan-1-one(894);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(methyl(propyl)amino)propan-1-one(895);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(isopropyl(methyl)amino)propan-1-one(896);2-((3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-oxopropyl)(methyl)amino)-N,N-dimethylacetamide(897);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-((2-methoxyethyl)(methyl)amino)propan-1-one(898);(R)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(3-hydroxypyrrolidin-1-yl)propan-1-one (899);3-(4,4-difluoropiperidin-1-yl)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one (900);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-((2-methoxyethyl)amino)propan-1-one(901);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(isopropylamino)propan-1-one(902);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(ethylamino)propan-1-one(903);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(piperidin-1-yl)propan-1-one(904);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(methylamino)propan-1-one(905);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(2,6-dimethylmorpholino)propan-1-one(906);1-(3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-oxopropyl)-N,N-diethylpiperidine-3-carboxamide(907);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(3,3-dimethylpiperidin-1-yl)propan-1-one(908);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(4-hydroxypiperidin-1-yl)propan-1-one (909);3-(azepan-1-yl)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one (910);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(2-(methoxymethyl)pyrrolidin-1-yl)propan-1-one (911);1-(3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-oxopropyl)piperidine-4-carboxamide(912);4-(3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-oxopropyl)piperazin-2-one (913);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-((2-hydroxyethyl)(methyl)amino)propan-1-one(914);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(4-methoxypiperidin-1-yl)propan-1-one(915); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one(916);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(2-(hydroxymethyl)pyrrolidin-1-yl)propan-1-one (917);3-(cyclobutylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one(918);3-(cyclopentylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one(919);3-(cyclohexylamino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one(920);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(3-fluoropyrrolidin-1-yl)propan-1-one(921);(S)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(3-hydroxypyrrolidin-1-yl)propan-1-one (922);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(3-hydroxypyrrolidin-1-yl)propan-1-one(923);3-(cyclohexyl(methyl)amino)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propan-1-one(924);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-((2-fluoroethyl)amino)propan-1-one(925);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-(neopentylamino)propan-1-one(926); azetidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(927); 2-aminoethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(928); (R)-pyrrolidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(929); piperidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(930); (S)-pyrrolidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(931); piperidin-3-ylmethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(932); (S)-pyrrolidin-2-ylmethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(933); 3-aminopropyl 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(934); piperidin-4-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(935); piperidin-4-ylmethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(936); pyrrolidin-2-ylmethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(937-938); (R)-pyrrolidin-3-ylmethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(939); pyrrolidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(940); azetidin-3-ylmethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(941); (S)-(1-methylpyrrolidin-2-yl) methyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (942); 2-(dimethylamino)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(943); 2-(1H-imidazol-1-yl)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(944); 1-isopropylpyrrolidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(945); 2-(1,1-dioxidothiomorpholino)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(946); 2-(piperidin-1-yl)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(947); 2-(pyrrolidin-1-yl)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(948); 2-(diethylamino)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(949); (1-(2-methoxyethyl)pyrrolidin-3-yl)methyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(950); 2-(4-methylpiperazin-1-yl)ethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(951); 2-morpholinoethyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(952); (R)-(1-methylpyrrolidin-2-yl)methyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(953); 1-methylpyrrolidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(954); 1-(2-methoxyethyl)azetidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(955); 1-propylazetidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(956);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-methylpiperazin-1-yl)methanone(957);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone(958);N-(3-aminopropyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxamide(959);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)methanone((960);(R)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(pyrrolidin-3-yl)piperidine-1-carboxamide(961);N-(2-aminoethyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-H-indol-5-yl)piperidine-1-carboxamide(962);4-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpiperazin-2-one(963);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(piperidin-3-yl)piperidine-1-carboxamide(964);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-propylpiperazin-1-yl)methanone(965);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(piperidin-2-ylmethyl)piperidine-1-carboxamide (966);(3-aminoazetidin-1-yl)(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methanone(967);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(pyrrolidin-3-yl)piperidine-1-carboxamide (968);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-(pyridin-4-yl)piperazin-1-yl)methanone(969);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(piperidin-4-ylmethyl)piperidine-1-carboxamide(970);(S)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(pyrrolidin-3-yl)piperidine-1-carboxamide(971);N-(2-aminoethyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-methylpiperidine-1-carboxamide(972); (4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-TH-indol-5-yl)piperidin-1-yl)(4-isopropylpiperazin-1-yl)methanone (973);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(2-(pyrrolidin-1-yl)ethyl)piperidine-1-carboxamide(974);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-((1-(2-methoxyethyl)pyrrolidin-2-yl)methyl)piperidine-1-carboxamide (975);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)piperidine-1-carboxamide (976);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-((1-methylpyrrolidin-2-yl)methyl)piperidine-1-carboxamide(977);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(2-(dimethylamino)ethyl)piperidine-1-carboxamide(978); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(2-morpholinoethyl)piperidine-1-carboxamide (979);4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-N-(2-(piperidin-1-yl)ethyl)piperidine-1-carboxamide(980);6-(3-isopropyl-5-(1-(pyridin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(986);1-(6-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)pyridin-3-yl)-N,N-dimethylmethanamine(987);1-(2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)pyridin-4-yl)-N,N-dimethylmethanamine(988); or6-(3-isopropyl-5-(1-(pyrimidin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(989).

One embodiment provides a compound of Formula (I-6) or a salt thereof,wherein R₁ is —CH(CH₃)₂; m is zero; n is zero, and R₃ is defined in thefirst aspect or the second aspect. Compounds of this embodiment have thestructure of Formula (I-6a)

Included in this embodiment are compounds in which R₃ is—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y) wherein each R_(x) is independently Hor —CH₃; and each R_(x) is independently H or —CH₃. Also included inthis embodiment are compounds in which R₃ is —CH₂C(O)NH₂,—CH₂C(O)NH(CH₃), or —CH₂C(O)N(CH₃)₂.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from:

Included in this embodiment is2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (15). Also included in this embodiment is one or more salts of2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (15).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-7):

wherein R₂ is F, Cl, —CN, —NH₂, —CH₂CH₃, —CH(CH₃)₂, —CF₃, C₁₋₃hydroxyalkyl, —CH₂CN, —CH₂OCH₂CH₃, —OCH₂F, —OCH₂CH₃, —OCH₂CH(CH₃)₂,—OCH₂CH₂OH, —OCH₂CH₂OC(O)CH₃, —NH(CH₂CH₃), —NH(CH₂CF₃),—NH(CH₂C(CH₃)₂OH), —NHCH₂(phenyl), —NHS(O)₂(cyclopropyl), cyclopropyl,morpholinyl, methyl-piperazinyl, or dioxothiomorpholinyl; and R₁, R₃,R₄, R₅, m, and n are defined in the first aspect or the second aspect.Included in this embodiment are compounds in which R₁ is —CH(CH₃)₂.Included in this embodiment are compounds in which R₃ is H, C₃₋₄ alkyl,C₁₋₂ cyanoalkyl, —CH₂C(CH₃)₂OH, —CH₂C(O)N(CH₃)₂, —CH₂C(O)NH(CH₃),—CH₂C(O)NH₂, —CH₂CH₂NHS(O)₂CH₃, —CH₂CH₂S(O)₂CH₃, —CH₂CH₂S(O)₂NH₂,—C(O)CH₂CF₃, —C(O)CH₂CH₂OH, —C(O)CH(CH₃)OH, —C(O)CH₂CH(CH₃)OH,—C(O)CH₂C(CH₃)₂OH, —C(O)CH₂OCH₃, —C(O)CH₂CH₂OCH₃, —C(O)CH₂NH(CH₃),—C(O)CH₂N(CH₃)₂, —C(O)CH₂N(CH₃)(CH₂CH₃), —C(O)CH₂N(CH₃)CH(CH₃)₂,—C(O)CH₂CH₂N(CH₃)₂, or -L₁-A; L₁ is —CH₂—, —CH₂CH₂—, —C(O)—, —C(O)CH₂—,—C(O)CH₂CH₂—, —C(O)CH₂N(CH₃)—, —CH₂C(O)—; and A is cyclopropyl,dioxoisothiazolidinyl, dioxotetrahydrothiopyranyl, morpholinyl,oxetanyl, piperidinyl, pyrazinyl, pyrazolyl, pyrimidinyl,tetrahydrofuranyl, tetrahydropyranyl, tetrazolyl, thiadiazolyl,thiazolyl, or triazolyl, each substituted with -L₂-R_(a); L₂ is a bond;and R_(a) is H, —CN, —CH₃, —CF₃, or —OCH₃. Also included in thisembodiment are compounds in which R₁ is —CH(CH₃)₂; m is zero, and n iszero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from8-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (94);8-isopropyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(95);8-(ethoxymethyl)-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(99);2-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(100);1-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol(103);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile(111);8-fluoro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(112);(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(113);2-((6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethan-1-ol(114);2-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol (115);2-((6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethylacetate (116);8-chloro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(118);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(128);8-ethoxy-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(132);8-isobutoxy-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(136);4-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine (143);N-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine (144);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-N-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine(145);1-((6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)amino)-2-methylpropan-2-ol(146);N-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)cyclopropanesulfonamide (147);4-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)thiomorpholine1,1-dioxide (148);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyridine(149);8-cyclopropyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (151);N-benzyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine(159);8-(difluoromethoxy)-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(160);2-(4-(2-(8-(ethoxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(163);2-(4-(2-(8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(193); 8-fluoro-6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (194);2-(4-(2-(8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(195);2-(4-(2-(8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (196);2-(4-(2-(8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(197);3-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propanenitrile (211);2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(212);2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (213);2-(6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(214);N-(2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethyl)methanesulfonamide(215);2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(216);2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (217);2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-ispropyl-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(218);N-(2-(4-(2-(8-cyano-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethyl)methanesulfonamide (220);6-(5-(1-(2-hydroxy-2-methylpropyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile(221);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile(222);6-(5-(1-(cyanomethyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile(223);2-(4-(2-(8-cyano-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(224);2-(4-(2-(8-(1-hydroxyethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(225);2-(4-(2-(8-(cyanomethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(228);2-(4-(2-(8-(1-hydroxyethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(229);2-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(231);2-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(232);(6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (233);2-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(234);3-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)oxetane-3-carbonitrile(235);2-(4-(2-(8-(2-hydroxyethoxy)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(236);2-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(250);2-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(251);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(252);2-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile (253);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (254);2-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(268);2-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(269);1-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(270);2-(4-(2-(8-isobutoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(278);2-(4-(2-(8-isobutoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(279);2-(4-(2-(8-chloro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(280); 2-(4-(2-(8-chloro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(281);1-(4-(2-(8-chloro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(282);2-(4-(3-isopropyl-2-(8-morpholino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(291);2-(4-(3-isopropyl-2-(8-morpholino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(292);2-(4-(2-(8-ethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(293); 2-(4-(2-(8-ethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(294);2-(4-(3-isopropyl-2-(8-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(295);2-(4-(3-isopropyl-2-(8-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(296); 2-(4-(2-(8-(ethylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(297);2-(4-(3-isopropyl-2-(8-((2,2,2-trifluoroethyl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(298);2-(4-(3-isopropyl-2-(8-((2,2,2-trifluoroethyl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(299); 2-(4-(2-(8-((2-hydroxy-2-methylpropyl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (300);2-(4-(2-(8-((2-hydroxy-2-methylpropyl)amino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(301);2-(4-(2-(8-(cyclopropanesulfonamido)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (307);2-(4-(2-(8-(1,1-dioxidothiomorpholino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(308);2-(4-(2-(8-(1,1-dioxidothiomorpholino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(309);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4] triazolo[1,5-a]pyridine (310);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyridine (311);2-(4-(2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(319);2-(4-(2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(320);8-cyclopropyl-6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(321);1-(4-(2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(322);2-(4-(2-(8-(difluoromethoxy)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(347);2-(4-(2-(8-(benzylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(348);8-fluoro-6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(468);8-fluoro-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(469);2-(6-(3-isopropyl-5-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(490);2-(6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(491);2-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(492);2-(6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(493);2-(6-(3-isopropyl-5-(1-(pyrimidin-2-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(494);2-(6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(495);4-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (496);2-(6-(5-(1-((1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol(497);2-(2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethyl)isothiazolidine 1,1-dioxide (498);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile(500);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile(501); 1-(6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol(502);1-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol(503);2-(6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)acetonitrile(506);(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(510);(6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(511);(6-(3-isopropyl-5-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(512);(6-(5-(1-((1H-1,2,3-triazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(513);4-(4-(2-(8-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (514);(6-(3-isopropyl-5-(1-((2-methoxypyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(515);(6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (516);(6-(3-isopropyl-5-(1-(pyrimidin-5-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(517);(6-(5-(1-((1,2,3-thiadiazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(518); (6-(3-isopropyl-5-(1-((2-methylpyrimidin-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(519);(6-(3-isopropyl-5-(1-(pyrimidin-2-ylmethyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (520);(6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(521);(6-(3-isopropyl-5-(1-((2-methyl-2H-tetrazol-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(522);(6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(523);(6-(3-isopropyl-5-(1-((5-methylpyrazin-2-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(524);2-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol(525);2-(6-(3-isopropyl-5-(1-((2-methylpyrimidin-5-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol(526); 2-(6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol(527);2-((6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethyl acetate (528);2-((6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethan-1-ol(529-530);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(549);4-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (550);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(551);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(552);6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(553);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(554);6-(3-isopropyl-5-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(555);6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(556-557);8-ethoxy-6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(571);8-ethoxy-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(572);4-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (573);4-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine (581);8-ethyl-6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(582);8-ethyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(583);6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-isopropyl-[1,2,4]triazolo[1,5-a]pyridine(584);8-isopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(585);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-N-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[1,5-a]pyridin-8-amine (586);N-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)cyclopropanesulfonamide(590);4-(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)thiomorpholine1,1-dioxide (591);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(4-methylpiperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyridine(592);8-cyclopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(593);2-(dimethylamino)-1-(4-(2-(8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(640);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(641);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(642);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methoxyethan-1-one(643);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-(piperidin-1-yl)propan-1-one(644);(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(tetrahydrofuran-2-yl)methanone (645);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methoxypropan-1-one(646);3-hydroxy-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one(647);3,3,3-trifluoro-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one(648);3-(dimethylamino)-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one (649);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(2-methylthiazol-4-yl)ethan-1-one(650);3-hydroxy-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methylbutan-1-one(651);2-hydroxy-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propan-1-one(652);(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-(trifluoromethyl)cyclopropyl)methanone (653);(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(oxetan-3-yl)methanone (654);1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-morpholinoethan-1-one(655);2-(dimethylamino)-1-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(680);1-(4-(2-(8-ethoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(681); 2-(dimethylamino)-1-(4-(2-(8-isobutoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(684);(S)-1-(4-(2-(8-chloro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(685);1-(4-(2-(8-chloro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(686);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-morpholino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(690);2-(dimethylamino)-1-(4-(2-(8-(1,1-dioxidothiomorpholino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(691);1-(4-(2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(696);1-(4-(2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(697);2-(isopropyl(methyl)amino)-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (777);2-(ethyl(methyl)amino)-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (778);2-(cyclopropyl(methyl)amino)-1-(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(779);2-(4-(2-(8-(2-hydroxypropan-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one(850); and2-(4-(2-(8-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(990).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-8):

wherein each R₂ is independently F, Cl, —NH₂, C₁₋₂ alkyl, —CF₃, —OCH₃,—OCH₂CH₃, —OCHF₂, cyclopropyl, or morpholinyl; and R₁, R₃, R₄, R₅, m,and n are defined in the first aspect or the second aspect. Included inthis embodiment are compounds in which R₁ is —CH₂CH₃, —CH(CH₃)₂, or—CH₂CHF₂. Included in this embodiment are compounds in which R₃ is H,—CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₂OH, —CH₂C(O)NH(CH₃),—CH₂C(O)N(CH₃)₂, —C(O)CH₂CH(CH₃)OH, —C(O)CH₂C(CH₃)₂OH, —C(O)CH₂NH(CH₃),—C(O)CH₂N(CH₃)₂, or -L₁-A; L₁ is —CH₂—, —C(O)—, or —CH₂C(O)—; and A isdioxotetrahydrothiopyranyl, dioxothiomorpholinyl, imidazolyl,morpholinyl, oxetanyl, pyrazolyl, pyrrolidinyl, tetrahydrofuranyl, ortetrahydropyranyl, each substituted with -L₂-R_(a) and zero to 1 R_(b);L₂ is a bond; R_(a) is H, —OH, —CH₃, or —C(O)OC(CH₃)₃; and R_(b) is —OH.Also included in this embodiment are compounds in which R₁ is —CH(CH₃)₂;m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from8-chloro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(96);8-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(97);6-(3-ethyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine(109);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(120);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(122);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(124);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(125);8-fluoro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(126);7-fluoro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(127);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(133);8-(difluoromethoxy)-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(134);8-ethoxy-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(135);8-chloro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(138);8-cyclopropyl-6-(3-isopropyl-5-(piperidin-4-yl)-H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(141);6-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(142);4-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine (150);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(153);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(154);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(155);6-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (162);2-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(237);2-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(238);1-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(239);2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(244);2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(245);1-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(246);2-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(247);2-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(248);1-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(249);2-(4-(3-(2,2-difluoroethyl)-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(255);2-(4-(3-(2,2-difluoroethyl)-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(256);2-(4-(2-(2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(257);2-(4-(2-(2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(258); 2-(4-(3-isopropyl-2-(2-methyl-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(259);2-(4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(260);2-(4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(261);1-(4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(262);2-(4-(3-isopropyl-2-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(271);2-(4-(3-isopropyl-2-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(272);1-(4-(3-isopropyl-2-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(273);2-(4-(2-(8-(difluoromethoxy)-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (274);2-(4-(2-(8-(difluoromethoxy)-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(275);2-(4-(2-(8-ethoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(276);2-(4-(2-(8-ethoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(277);2-(4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (283);1-(4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(284);2-(4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (285);2-(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(312);2-(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(313);1-(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(314);2-(4-(3-isopropyl-2-(2-methyl-8-morpholino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(315);2-(4-(3-isopropyl-2-(2-methyl-8-morpholino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(316);2-(4-(3-isopropyl-2-(8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(317);2-(4-(3-isopropyl-2-(8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(318);2-(4-(2-(8-cyclopropyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(323);1-(4-(2-(8-cyclopropyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(324);2-(4-(2-(8-cyclopropyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(325);2-(4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(345);2-(4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(346);2-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylethan-1-amine(531);6-(3-isopropyl-5-(1-((2-methyl-1H-imidazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (532);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(533);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (534);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(535);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (542);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(543);6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(544);4-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (545);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(546);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(547);4-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (548);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(558);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(559); 6-(3-isopropyl-5-(1-((1-methyl-1H-pyrazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(560);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (574);6-(3-isopropyl-5-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (575-576);8-ethyl-6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (577);8-ethyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(578);8-cyclopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(594);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridine (599);2-(dimethylamino)-1-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(612);(R)-3-hydroxy-1-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-one (613);3-hydroxy-1-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methylbutan-1-one(614);((2S,3R)-3-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(615);((2S,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(616);(S)-3-hydroxy-1-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-one (617);1-(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(618);1-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(629);1-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(630);(S)-1-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one (631);1-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxy-3-methylbutan-1-one(632);(R)-1-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one (633); tert-butyl(2S,3R)-2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carbonyl)-3-hydroxypyrrolidine-1-carboxylate(634);(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)((2S,3R)-3-hydroxypyrrolidin-2-yl)methanone(635);(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone (636);(S)-1-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(637);1-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one (638);1-(4-(2-(2,7-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(639);1-(4-(3-(2,2-difluoroethyl)-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(656);(R)-1-(4-(3-(2,2-difluoroethyl)-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(657);1-(4-(3-(2,2-difluoroethyl)-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-hydroxy-3-methylbutan-1-one(658);1-(4-(3-(2,2-difluoroethyl)-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(659);1-(4-(2-(2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(660);1-(4-(2-(2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(661);1-(4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(662);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(682);1-(4-(3-isopropyl-2-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (683);2-(dimethylamino)-1-(4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(687);1-(4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (688);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(692);1-(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(693);(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpiperidin-4-yl)methanone (694);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (695);1-(4-(2-(8-cyclopropyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(698);1-(4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(708);(S)-1-(4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(709);1-(4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-hydroxy-3-methylbutan-1-one(710);1-(4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(711);2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one(851);2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one(852); and2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one(853).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-9):

wherein R₂ is F, Cl, —CH₂CH₃, —CF₃, —OCH₃, —CH₂OH, —CH₂OCH₃, orcyclopropyl; and R₁, R₃, R₄, R₅, m, and n are defined in the firstaspect or the second aspect. Included in this embodiment are compoundsin which R₁ is —CH(CH₃)₂. Included in this embodiment are compounds inwhich R₃ is H, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₂OH, —CH₂C(O)NH(CH₃),—CH₂C(O)N(CH₃)₂, —C(O)CH₂CH(CH₃)OH, —C(O)CH₂C(CH₃)₂OH, —C(O)CH₂NH(CH₃),—C(O)CH₂N(CH₃)₂, or -L₁-A; L₁ is —CH₂—, —CH₂C(O)NHCH₂—, or —CH₂C(O)—;and A is azetidinyl, dioxothiomorpholinyl, morpholinyl, oxetanyl,tetrahydropyranyl, or triazolyl, each substituted with -L₂-R_(a); L₂ isa bond; R_(a) is H or —CH₃. Also included in this embodiment arecompounds in which R₁ is —CH(CH₃)₂; m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from tert-butyl4-(2-(8-ethyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(98);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(101);8-fluoro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(102);(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (104);8-fluoro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(106);8-fluoro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(107);8-chloro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(119);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(140);8-cyclopropyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(152);2-(4-(3-isopropyl-2-(8-(methoxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(219);2-(4-(2-(8-(hydroxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(226);2-(4-(2-(8-(hydroxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile (227);2-(4-(2-(8-chloro-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(286);1-(4-(2-(8-chloro-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(287);2-(4-(2-(8-chloro-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(288);2-(4-(2-(8-chloro-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(289);8-chloro-6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(290);2-(4-(2-(8-ethyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (302);2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(303);2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(304);1-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(305);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (306);2-(4-(2-(8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(326);2-(4-(2-(8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(327);1-(4-(2-(8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(328);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-7-methyl-[1,2,4]triazolo [1,5-a]pyridine (499);(6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol (504); (6-(5-(1-((1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol(505);8-fluoro-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(507);8-chloro-6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(579);8-chloro-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (580);8-ethyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(587); 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(588);6-(3-isopropyl-5-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (589);8-cyclopropyl-6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(595);1-(4-(2-(8-chloro-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(689); 1-(4-(2-(8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(699);1-(4-(2-(8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(700);2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-((3-methyloxetan-3-yl)methyl)acetamide(876); 2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(3-methyloxetan-3-yl)acetamide (877);1-(azetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (878);N-ethyl-2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (879);1-(1,1-dioxidothiomorpholino)-2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl) ethan-1-one (880);and2-(4-(3-isopropyl-2-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one(881).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-10):

wherein R₂ is —CH₃, —OCH₃, or —CH₂OH; and R₁, R₃, R₄, R₅, m, and n aredefined in the first aspect or the second aspect. Included in thisembodiment are compounds in which R₁ is —CH(CH₃)₂. Included in thisembodiment are compounds in which R₃ is H, —CH₂CN, —CH₂C(O)NH₂,—CH₂C(O)N(CH₃)₂, —CH₂(triazolyl), or oxetanyl. Also included in thisembodiment are compounds in which R₁ is —CH(CH₃)₂; m is zero; and n iszero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol (108);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methoxy-[1,2,4]triazolo[1,5-a]pyridine(131); 2-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (192);2-(4-(2-(7-(hydroxymethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(230);2-(4-(3-isopropyl-2-(7-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(267); (6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol(508); and(6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol(509).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound has the structure of Formula (I-11):

wherein R₁, R₃, R₄, R₅, m, and n are defined in the first aspect or thesecond aspect. Included in this embodiment are compounds in which R₁ is—CH(CH₃)₂. Included in this embodiment are compounds in which R₃ is—CH₂CN, —CH₂C(O)N(CH₃)₂, —CH₂CH₂S(O)₂CH₃, —CH₂(methyltriazolyl),—C(O)CH₂N(CH₃)₂, dioxotetrahydrothiopyranyl, oxetanyl, ortetrahydropyranyl. Also included in this embodiment are compounds inwhich R₁ is —CH(CH₃)₂; m is zero, and n is zero.

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from2-(4-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(207);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(208);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine(209);2-(4-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(210);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(487);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(488);4-(4-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran1,1-dioxide (489); and1-(4-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(611).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from2-(6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-8-yl)acetonitrile(105); and6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-5-methyl-[1,2,4]triazolo[1,5-a]pyridine(123);

One embodiment provides a compound of Formula (I) or a salt thereof,wherein said compound is selected from6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (1);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine hydrochloride (2);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(3);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(4);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(5);6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine (6);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(7);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile(8);3-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)propanenitrile (9);6-(5-(1-butylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(10);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(11);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(12);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile(13);3-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)propanenitrile(14);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide (15);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(16); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(17);6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine(18);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)ethane-1-sulfonamide(19);4-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (20);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetonitrile (21);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (22);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(23);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methylpropan-2-ol(24);2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(25);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(26);6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(27);6-(3-isopropyl-5-(1-propylpiperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(28);6-(5-(1-isobutylpiperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(29); 6-(5-(1-((1H-pyrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (30);4-((4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methyl)oxazole (31);6-(5-(1-((1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(32);6-(5-(1-((4H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (33);6-(5-(1-((1H-tetrazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (34);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(35);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(36);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)tetrahydro-2H-thiopyran 1,1-dioxide (37);6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-1-[1,2,4]triazolo[1,5-a]pyridine(38);6-(5-(1-((1H-1,2,3-triazol-5-yl)methyl)piperidin-4-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridine (39);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(40);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(41); 6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(42);6-(3-isopropyl-5-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (43); 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(44);6-(3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (45);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (46); 1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (47);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (48);3-(4-(3-isopropyl-2-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-oxopropanenitrile(49);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one(50);1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(51);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methoxyethan-1-one(52);(S)-1-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-3-hydroxybutan-1-one(53);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-4-oxobutanenitrile (54);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylcyclopropyl)methanone(55);(S)-azetidin-2-yl(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone (56);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(57);(S)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)propan-1-one(58);(R)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)propan-1-one(59);(S)-3-hydroxy-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-one (60);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-methoxypropan-1-one(61);1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (62); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-methoxyethan-1-one(63);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(3-methyloxetan-3-yl)methanone(64);2-ethyl-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)butan-1-one (65);1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one(66);2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(67);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-morpholinoethan-1-one(68);2-(tert-butylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(69);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(isopropylamino)ethan-1-one(70);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-((2-methoxyethyl)amino)ethan-1-one(71);1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-(propylamino)ethan-1-one(72); 2-(isopropyl(methyl)amino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one (73);1-(1,1-dioxido-1,2,4-thiadiazinan-4-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(74);N-cyclopropyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(75);N-ethyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(76);(S)-1-(3-hydroxypiperidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazol-([1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(77);N-cyclobutyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(78);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)ethan-1-one (79);N,N-diethyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide(80);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-propylacetamide(81);(R)-1-(3-hydroxypiperidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(82);(S)-1-(3-hydroxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(83);(R)-1-(3-hydroxypyrrolidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(84); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(4-(2-methoxyethyl) piperazin-1-yl)ethan-1-one (85);1-(azetidin-1-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(86);N-isopropyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetamide (87);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-morpholinoethan-1-one(88);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(piperidin-1-yl)ethan-1-one (89);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one(90);1-(1,1-dioxidothiomorpholino)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one(91);2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-(3-methyloxetan-3-yl)acetamide (92); andN-cyclopropyl-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide(93).

One embodiment provides a compound of Formula (I) or a salt thereof,wherein R₁ is —CH(CH₃)₂; each R₂ is independently —CH₃ or —OCH₃; R₃ is—(CR_(x)R_(x))₁₋₂C(O)NR_(y)R_(y); m is zero, n is zero, p is 1 or 2;each R_(x) is independently H or —CH₃; and each R_(y) is independently Hor —CH₃. Included in this embodiment are compounds in which R₃ is—CH₂C(O)NR_(y)R_(y). Also included in this embodiment are compoundshaving the structure of Formula (I-4b) or Formula (I-6b) in which eachR_(y) is H or —CH₃:

Additionally, included in this embodiment are compounds in which R₃ is—CH₂C(O)NH₂ or —CH₂C(O)N(CH₃)₂.

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof. The inventionencompasses all combinations of the aspects and/or embodiments of theinvention noted herein. It is understood that any and all embodiments ofthe present invention may be taken in conjunction with any otherembodiment or embodiments to describe additional embodiments. It is alsoto be understood that each individual element of the embodiments ismeant to be combined with any and all other elements from any embodimentto describe an additional embodiment.

Definitions

The features and advantages of the invention may be more readilyunderstood by those of ordinary skill in the art upon reading thefollowing detailed description. It is to be appreciated that certainfeatures of the invention that are, for clarity reasons, described aboveand below in the context of separate embodiments, may also be combinedto form a single embodiment. Conversely, various features of theinvention that are, for brevity reasons, described in the context of asingle embodiment, may also be combined so as to form sub-combinationsthereof. Embodiments identified herein as exemplary or preferred areintended to be illustrative and not limiting.

Unless specifically stated otherwise herein, references made in thesingular may also include the plural. For example, “a” and “an” mayrefer to either one, or one or more.

As used herein, the phrase “compounds” refers to at least one compound.For example, a compound of Formula (I) includes a compound of Formula(I) and two or more compounds of Formula (I).

Unless otherwise indicated, any heteroatom with unsatisfied valences isassumed to have hydrogen atoms sufficient to satisfy the valences.

The definitions set forth herein take precedence over definitions setforth in any patent, patent application, and/or patent applicationpublication incorporated herein by reference.

Listed below are definitions of various terms used to describe thepresent invention. These definitions apply to the terms as they are usedthroughout the specification (unless they are otherwise limited inspecific instances) either individually or as part of a larger group.

Throughout the specification, groups and substituents thereof may bechosen by one skilled in the field to provide stable moieties andcompounds.

In accordance with a convention used in the art,

is used in structural formulas herein to depict the bond that is thepoint of attachment of the moiety or substituent to the core or backbonestructure.

The terms “halo” and “halogen,” as used herein, refer to F, Cl, Br, andI.

The term “cyano” refers to the group —CN.

The term “amino” refers to the group —NH₂.

The term “oxo” refers to the group ═O.

The term “alkyl” as used herein, refers to both branched andstraight-chain saturated aliphatic hydrocarbon groups containing, forexample, from 1 to 12 carbon atoms, from 1 to 6 carbon atoms, and from 1to 4 carbon atoms. Examples of alkyl groups include, but are not limitedto, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and i-propyl), butyl(e.g., n-butyl, i-butyl, sec-butyl, and t-butyl), and pentyl (e.g.,n-pentyl, isopentyl, neopentyl), n-hexyl, 2-methylpentyl, 2-ethylbutyl,3-methylpentyl, and 4-methylpentyl. When numbers appear in a subscriptafter the symbol “C”, the subscript defines with more specificity thenumber of carbon atoms that a particular group may contain. For example,“C₁₋₆ alkyl” denotes straight and branched chain alkyl groups with oneto six carbon atoms.

The term “fluoroalkyl” as used herein is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupssubstituted with one or more fluorine atoms. For example, “C₁₋₄fluoroalkyl” is intended to include C₁, C₂, C₃, and C₄ alkyl groupssubstituted with one or more fluorine atoms. Representative examples offluoroalkyl groups include, but are not limited to, —CF₃ and —CH₂CF₃.

The term “chloroalkyl” as used herein is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupssubstituted with one or more chlorine atoms. For example, “C₁₋₄chloroalkyl” is intended to include C₁, C₂, C₃, and C₄ alkyl groupssubstituted with one or more chlorine atoms. Representative examples offluoroalkyl groups include, but are not limited to, —CCl₃ and —CH₂CCl₃.

The term “cyanoalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more cyano groups. Forexample, “cyanoalkyl” includes —CH₂CN, —CH₂CH₂CN, and C₁₋₄ cyanoalkyl.

The term “aminoalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more amine groups. Forexample, “aminoalkyl” includes —CH₂NH₂, —CH₂CH₂NH₂, and C₁₋₄ aminoalkyl.

The term “hydroxyalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more hydroxyl groups. Forexample, “hydroxyalkyl” includes —CH₂OH, —CH₂CH₂OH, and C₁₋₄hydroxyalkyl.

The term “hydroxy-fluoroalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more hydroxyl groups andone or more fluorine atoms. For example, “hydroxy-fluoroalkyl” includes—CHFCH₂OH, —CH₂CHFC(CH₃)₂OH, and C₁₋₄ hydroxy-fluoroalkyl.

The term “cycloalkyl,” as used herein, refers to a group derived from anon-aromatic monocyclic or polycyclic hydrocarbon molecule by removal ofone hydrogen atom from a saturated ring carbon atom. Representativeexamples of cycloalkyl groups include, but are not limited to,cyclopropyl, cyclopentyl, and cyclohexyl. When numbers appear in asubscript after the symbol “C”, the subscript defines with morespecificity the number of carbon atoms that a particular cycloalkylgroup may contain. For example, “C₃-C₆ cycloalkyl” denotes cycloalkylgroups with three to six carbon atoms.

The term “alkoxy,” as used herein, refers to an alkyl group attached tothe parent molecular moiety through an oxygen atom, for example, methoxygroup (—OCH₃). For example, “C₁₋₃ alkoxy” denotes alkoxy groups with oneto three carbon atoms.

The terms “fluoroalkoxy” and “—O(fluoroalkyl)” represent a fluoroalkylgroup as defined above attached through an oxygen linkage (—O—). Forexample, “C₁₋₄ fluoroalkoxy” is intended to include C₁, C₂, C₃, and C₄fluoroalkoxy groups.

The term “alkoxyalkoxy,” as used herein, refers to an alkoxy groupattached through its oxygen atom to a carbon atom in a second alkoxygroup, which is attached to the parent molecular moiety through anoxygen atom, for example, methoxymethoxy group (—OCH₂OCH₃). For example,“C₂₋₄ alkoxyalkoxy” denotes alkoxyalkoxy groups with two to four carbonatoms, such as —OCH₂OCH₃, —OCH₂CH₂OCH₃, —OCH₂OCH₂CH₃, and—OCH₂CH₂OCH₂CH₃.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

The compounds of Formula (I) can be provided as amorphous solids orcrystalline solids. Lyophilization can be employed to provide thecompounds of Formula (I) as amorphous solids.

It should further be understood that solvates (e.g., hydrates) of thecompounds of Formula (I) are also within the scope of the presentinvention. The term “solvate” means a physical association of a compoundof Formula (I) with one or more solvent molecules, whether organic orinorganic. This physical association includes hydrogen bonding. Incertain instances the solvate will be capable of isolation, for examplewhen one or more solvent molecules are incorporated in the crystallattice of the crystalline solid. “Solvate” encompasses bothsolution-phase and isolable solvates. Exemplary solvates includehydrates, ethanolates, methanolates, isopropanolates, acetonitrilesolvates, and ethyl acetate solvates. Methods of solvation are known inthe art.

Various forms of prodrugs are well known in the art and are describedin:

-   a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al.,    Ch 31, (Academic Press, 1996);-   b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985);-   c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson    and H. Bundgaard, eds. Ch 5, pgs 113-191 (Harwood Academic    Publishers, 1991); and-   d) Hydrolysis in Drug and Prodrug Metabolism, Bernard Testa and    Joachim M. Mayer, (Wiley-VCH, 2003).

In addition, compounds of Formula (I), subsequent to their preparation,can be isolated and purified to obtain a composition containing anamount by weight equal to or greater than 99% of a compound of Formula(I) (“substantially pure”), which is then used or formulated asdescribed herein. Such “substantially pure” compounds of Formula (I) arealso contemplated herein as part of the present invention.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent. The present invention is intended toembody stable compounds.

“Therapeutically effective amount” is intended to include an amount of acompound of the present invention alone or an amount of the combinationof compounds claimed or an amount of a compound of the present inventionin combination with other active ingredients effective to act as aninhibitor to TLR7/8/9, or effective to treat or prevent autoimmuneand/or inflammatory disease states, such as SLE, IBD, multiple sclerosis(MS), and Sjögren's syndrome, and rheumatoid arthritis.

As used herein, “treating” or “treatment” cover the treatment of adisease-state in a mammal, particularly in a human, and include: (a)preventing the disease-state from occurring in a mammal, in particular,when such mammal is predisposed to the disease-state but has not yetbeen diagnosed as having it; (b) inhibiting the disease-state, i.e.,arresting its development; and/or (c) relieving the disease-state, i.e.,causing regression of the disease state.

The compounds of the present invention are intended to include allisotopes of atoms occurring in the present compounds. Isotopes includethose atoms having the same atomic number but different mass numbers. Byway of general example and without limitation, isotopes of hydrogeninclude deuterium (D) and tritium (T). Isotopes of carbon include ¹³Cand ¹⁴C. Isotopically-labeled compounds of the invention can generallybe prepared by conventional techniques known to those skilled in the artor by processes analogous to those described herein, using anappropriate isotopically-labeled reagent in place of the non-labeledreagent otherwise employed. For example, methyl (—CH₃) also includesdeuterated methyl groups such as —CD₃.

Utility

The human immune system has evolved to defend the body frommicro-organisms, viruses, and parasites that can cause infection,disease or death.

Complex regulatory mechanisms ensure that the various cellularcomponents of the immune system target the foreign substances ororganisms, while not causing permanent or significant damage to theindividual. While the initiating events are not well understood at thistime, in autoimmune disease states the immune system directs itsinflammatory response to target organs in the afflicted individual.Different autoimmune diseases are typically characterized by thepredominate or initial target organ or tissues affected; such as thejoint in the case of rheumatoid arthritis, the thyroid gland in the caseof Hashimoto's thyroiditis, the central nervous system in the case ofmultiple sclerosis, the pancreas in the case of type I diabetes, and thebowel in the case of inflammatory bowel disease.

The compounds of the invention inhibit signaling through Toll-likereceptor 7, or 8, or 9 (TLR7, TLR8, TLR9) or combinations thereof.Accordingly, compounds of Formula (I) have utility in treatingconditions associated with the inhibition of signaling through one ormore of TLR7, TLR8, or TLR9. Such conditions include TLR7, TLR8, or TLR9receptor associated diseases in which cytokine levels are modulated as aconsequence of intracellular signaling.

As used herein, the terms “treating” or “treatment” encompass thetreatment of a disease state in a mammal, particularly in a human, andinclude: (a) preventing or delaying the occurrence of the disease statein a mammal, in particular, when such mammal is predisposed to thedisease state but has not yet been diagnosed as having it; (b)inhibiting the disease state, i.e., arresting its development; and/or(c) achieving a full or partial reduction of the symptoms or diseasestate, and/or alleviating, ameliorating, lessening, or curing thedisease or disorder and/or its symptoms.

In view of their activity as selective inhibitors of TLR7, TLR8, orTLR9, compounds of Formula (I) are useful in treating TLR7, TLR8, orTLR9 family receptor associated diseases, but not limited to,inflammatory diseases such as Crohn's disease, ulcerative colitis,asthma, graft versus host disease, allograft rejection, chronicobstructive pulmonary disease; autoimmune diseases such as Graves'disease, rheumatoid arthritis, systemic lupus erythematosis, lupusnephritis, cutaneous lupus, psoriasis; auto-inflammatory diseasesincluding Cryopyrin-Associated Periodic Syndromes (CAPS), TNF ReceptorAssociated Periodic Syndrome (TRAPS), Familial Mediterranean Fever(FMF), adult onset stills, systemic onset juvenile idiopathic arthritis,gout, gouty arthritis; metabolic diseases including type 2 diabetes,atherosclerosis, myocardial infarction; destructive bone disorders suchas bone resorption disease, osteoarthritis, osteoporosis, multiplemyeloma-related bone disorder; proliferative disorders such as acutemyelogenous leukemia, chronic myelogenous leukemia; angiogenic disorderssuch as angiogenic disorders including solid tumors, ocularneovasculization, and infantile haemangiomas; infectious diseases suchas sepsis, septic shock, and Shigellosis; neurodegenerative diseasessuch as Alzheimer's disease, Parkinson's disease, cerebral ischemias orneurodegenerative disease caused by traumatic injury, oncologic andviral diseases such as metastatic melanoma, Kaposi's sarcoma, multiplemyeloma, and HIV infection and CMV retinitis, AIDS, respectively.

More particularly, the specific conditions or diseases that may betreated with the inventive compounds include, without limitation,pancreatitis (acute or chronic), asthma, allergies, adult respiratorydistress syndrome, chronic obstructive pulmonary disease,glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosis,scleroderma, chronic thyroiditis, Graves' disease, autoimmune gastritis,diabetes, autoimmune hemolytic anemia, autoimmune neutropenia,thrombocytopenia, atopic dermatitis, chronic active hepatitis,myasthenia gravis, multiple sclerosis, inflammatory bowel disease,ulcerative colitis, Crohn's disease, psoriasis, graft vs. host disease,inflammatory reaction induced by endotoxin, tuberculosis,atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis,Reiter's syndrome, gout, traumatic arthritis, rubella arthritis, acutesynovitis, pancreatic β-cell disease; diseases characterized by massiveneutrophil infiltration; rheumatoid spondylitis, gouty arthritis andother arthritic conditions, cerebral malaria, chronic pulmonaryinflammatory disease, silicosis, pulmonary sarcoidosis, bone resorptiondisease, allograft rejections, fever and myalgias due to infection,cachexia secondary to infection, keloid formation, scar tissueformation, ulcerative colitis, pyresis, influenza, osteoporosis,osteoarthritis, acute myelogenous leukemia, chronic myelogenousleukemia, metastatic melanoma, Kaposi's sarcoma, multiple myeloma,sepsis, septic shock, and Shigellosis; Alzheimer's disease, Parkinson'sdisease, cerebral ischemias or neurodegenerative disease caused bytraumatic injury; angiogenic disorders including solid tumors, ocularneovasculization, and infantile haemangiomas; viral diseases includingacute hepatitis infection (including hepatitis A, hepatitis B andhepatitis C), HIV infection and CMV retinitis, AIDS, ARC or malignancy,and herpes; stroke, myocardial ischemia, ischemia in stroke heartattacks, organ hypoxia, vascular hyperplasia, cardiac and renalreperfusion injury, thrombosis, cardiac hypertrophy, thrombin-inducedplatelet aggregation, endotoxemia and/or toxic shock syndrome,conditions associated with prostaglandin endoperoxidase syndase-2, andpemphigus vulgaris. Included in this embodiment are methods of treatmentin which the condition is selected from lupus including lupus nephritisand systemic lupus erythematosus (SLE), Crohn's disease, ulcerativecolitis, allograft rejection, rheumatoid arthritis, psoriasis,ankylosing spondylitis, psoriatic arthritis, and pemphigus vulgaris.Also included are methods of treatment in which the condition isselected from ischemia reperfusion injury, including cerebral ischemiareperfusions injury arising from stroke and cardiac ischemia reperfusioninjury arising from myocardial infarction. Another method of treatmentis one in which the condition is multiple myeloma.

In one embodiment, the compounds of Formula (I) are useful in treatingcancer, including Waldenstrom's Macroglobulinemia (WM), diffuse large Bcell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), cutaneousdiffuse large B cell lymphoma, and primary CNS lymphoma.

In addition, the TLR7, TLR8, or TLR9 inhibitors of the present inventioninhibit the expression of inducible pro-inflammatory proteins such asprostaglandin endoperoxide synthase-2 (PGHS-2), also referred to ascyclooxygenase-2 (COX-2), IL-1, IL-6, IL-18, chemokines. Accordingly,additional TLR7/8/9 associated conditions include edema, analgesia,fever and pain, such as neuromuscular pain, headache, pain caused bycancer, dental pain and arthritis pain. The inventive compounds also maybe used to treat veterinary viral infections, such as lentivirusinfections, including, but not limited to equine infectious anemiavirus; or retrovirus infections, including feline immunodeficiencyvirus, bovine immunodeficiency virus, and canine immunodeficiency virus.

The present invention thus provides methods for treating suchconditions, comprising administering to a subject in need thereof atherapeutically-effective amount of at least one compound of Formula (I)or a salt thereof. “Therapeutically effective amount” is intended toinclude an amount of a compound of the present invention that iseffective when administered alone or in combination to inhibitautoimmune disease or chronic inflammatory disease.

The methods of treating TLR7, TLR8, or TLR9 associated conditions maycomprise administering compounds of Formula (I) alone or in combinationwith each other and/or other suitable therapeutic agents useful intreating such conditions. Accordingly, “therapeutically effectiveamount” is also intended to include an amount of the combination ofcompounds claimed that is effective to inhibit TLR7, TLR8, or TLR9and/or treat diseases associated with TLR7, TLR8, or TLR9.

Exemplary of such other therapeutic agents include corticosteroids,rolipram, calphostin, cytokine-suppressive anti-inflammatory drugs(CSAIDs), Interleukin-10, glucocorticoids, salicylates, nitric oxide,and other immunosuppressants; nuclear translocation inhibitors, such asdeoxyspergualin (DSG); non-steroidal anti-inflammatory drugs (NSAIDs)such as ibuprofen, celecoxib and rofecoxib; steroids such as prednisoneor dexamethasone; antiviral agents such as abacavir; antiproliferativeagents such as methotrexate, leflunomide, FK506 (tacrolimus, PROGRAF®);anti-malarials such as hydroxychloroquine; cytotoxic drugs such asazathiprine and cyclophosphamide; TNF-α inhibitors such as tenidap,anti-TNF antibodies or soluble TNF receptor, and rapamycin (sirolimus orRAPAMUNE®) or derivatives thereof.

The above other therapeutic agents, when employed in combination withthe compounds of the present invention, may be used, for example, inthose amounts indicated in the Physicians' Desk Reference (PDR) or asotherwise determined by one of ordinary skill in the art. In the methodsof the present invention, such other therapeutic agent(s) may beadministered prior to, simultaneously with, or following theadministration of the inventive compounds. The present invention alsoprovides pharmaceutical compositions capable of treating TLR7/8/9receptor-associated conditions, including IL-1 family receptor-mediateddiseases as described above.

The inventive compositions may contain other therapeutic agents asdescribed above and may be formulated, for example, by employingconventional solid or liquid vehicles or diluents, as well aspharmaceutical additives of a type appropriate to the mode of desiredadministration (e.g., excipients, binders, preservatives, stabilizers,flavors, etc.) according to techniques such as those well known in theart of pharmaceutical formulation.

Accordingly, the present invention further includes compositionscomprising one or more compounds of Formula (I) and a pharmaceuticallyacceptable carrier.

A “pharmaceutically acceptable carrier” refers to media generallyaccepted in the art for the delivery of biologically active agents toanimals, in particular, mammals. Pharmaceutically acceptable carriersare formulated according to a number of factors well within the purviewof those of ordinary skill in the art. These include without limitationthe type and nature of the active agent being formulated; the subject towhich the agent-containing composition is to be administered; theintended route of administration of the composition; and, thetherapeutic indication being targeted. Pharmaceutically acceptablecarriers include both aqueous and non-aqueous liquid media, as well as avariety of solid and semi-solid dosage forms. Such carriers can includea number of different ingredients and additives in addition to theactive agent, such additional ingredients being included in theformulation for a variety of reasons, e.g., stabilization of the activeagent, binders, etc., well known to those of ordinary skill in the art.Descriptions of suitable pharmaceutically acceptable carriers, andfactors involved in their selection, are found in a variety of readilyavailable sources such as, for example, Remington's PharmaceuticalSciences, 17th Edition (1985), which is incorporated herein by referencein its entirety.

Compounds in accordance with Formula (I) can be administered by anymeans suitable for the condition to be treated, which can depend on theneed for site-specific treatment or quantity of Formula (I) compound tobe delivered.

Also embraced within this invention is a class of pharmaceuticalcompositions comprising a compound of Formula (I) and one or morenon-toxic, pharmaceutically-acceptable carriers and/or diluents and/oradjuvants (collectively referred to herein as “carrier” materials) and,if desired, other active ingredients. The compounds of Formula (I) maybe administered by any suitable route, preferably in the form of apharmaceutical composition adapted to such a route, and in a doseeffective for the treatment intended. The compounds and compositions ofthe present invention may, for example, be administered orally,mucosally, or parenterally including intravascularly, intravenously,intraperitoneally, subcutaneously, intramuscularly, and intrasternallyin dosage unit formulations containing conventional pharmaceuticallyacceptable carriers, adjuvants, and vehicles. For example, thepharmaceutical carrier may contain a mixture of mannitol or lactose andmicrocrystalline cellulose. The mixture may contain additionalcomponents such as a lubricating agent, e.g. magnesium stearate and adisintegrating agent such as crospovidone. The carrier mixture may befilled into a gelatin capsule or compressed as a tablet. Thepharmaceutical composition may be administered as an oral dosage form oran infusion, for example.

For oral administration, the pharmaceutical composition may be in theform of, for example, a tablet, capsule, liquid capsule, suspension, orliquid. The pharmaceutical composition is preferably made in the form ofa dosage unit containing a particular amount of the active ingredient.For example, the pharmaceutical composition may be provided as a tabletor capsule comprising an amount of active ingredient in the range offrom about 0.1 to 1000 mg, preferably from about 0.25 to 250 mg, andmore preferably from about 0.5 to 100 mg. A suitable daily dose for ahuman or other mammal may vary widely depending on the condition of thepatient and other factors, but, can be determined using routine methods.

Any pharmaceutical composition contemplated herein can, for example, bedelivered orally via any acceptable and suitable oral preparations.Exemplary oral preparations, include, but are not limited to, forexample, tablets, troches, lozenges, aqueous and oily suspensions,dispersible powders or granules, emulsions, hard and soft capsules,liquid capsules, syrups, and elixirs. Pharmaceutical compositionsintended for oral administration can be prepared according to anymethods known in the art for manufacturing pharmaceutical compositionsintended for oral administration. In order to provide pharmaceuticallypalatable preparations, a pharmaceutical composition in accordance withthe invention can contain at least one agent selected from sweeteningagents, flavoring agents, coloring agents, demulcents, antioxidants, andpreserving agents.

A tablet can, for example, be prepared by admixing at least one compoundof Formula (I) with at least one non-toxic pharmaceutically acceptableexcipient suitable for the manufacture of tablets. Exemplary excipientsinclude, but are not limited to, for example, inert diluents, such as,for example, calcium carbonate, sodium carbonate, lactose, calciumphosphate, and sodium phosphate; granulating and disintegrating agents,such as, for example, microcrystalline cellulose, sodium croscarmellose,corn starch, and alginic acid; binding agents, such as, for example,starch, gelatin, polyvinyl-pyrrolidone, and acacia; and lubricatingagents, such as, for example, magnesium stearate, stearic acid, andtalc. Additionally, a tablet can either be uncoated, or coated by knowntechniques to either mask the bad taste of an unpleasant tasting drug,or delay disintegration and absorption of the active ingredient in thegastrointestinal tract thereby sustaining the effects of the activeingredient for a longer period. Exemplary water soluble taste maskingmaterials, include, but are not limited to,hydroxypropyl-methylcellulose and hydroxypropyl-cellulose. Exemplarytime delay materials, include, but are not limited to, ethyl celluloseand cellulose acetate butyrate.

Hard gelatin capsules can, for example, be prepared by mixing at leastone compound of Formula (I) with at least one inert solid diluent, suchas, for example, calcium carbonate; calcium phosphate; and kaolin.

Soft gelatin capsules can, for example, be prepared by mixing at leastone compound of Formula (I) with at least one water soluble carrier,such as, for example, polyethylene glycol; and at least one oil medium,such as, for example, peanut oil, liquid paraffin, and olive oil.

An aqueous suspension can be prepared, for example, by admixing at leastone compound of Formula (I) with at least one excipient suitable for themanufacture of an aqueous suspension. Exemplary excipients suitable forthe manufacture of an aqueous suspension, include, but are not limitedto, for example, suspending agents, such as, for example, sodiumcarboxymethylcellulose, methylcellulose, hydroxypropylmethyl-cellulose,sodium alginate, alginic acid, polyvinyl-pyrrolidone, gum tragacanth,and gum acacia; dispersing or wetting agents, such as, for example, anaturally-occurring phosphatide, e.g., lecithin; condensation productsof alkylene oxide with fatty acids, such as, for example,polyoxyethylene stearate; condensation products of ethylene oxide withlong chain aliphatic alcohols, such as, for exampleheptadecaethylene-oxycetanol; condensation products of ethylene oxidewith partial esters derived from fatty acids and hexitol, such as, forexample, polyoxyethylene sorbitol monooleate; and condensation productsof ethylene oxide with partial esters derived from fatty acids andhexitol anhydrides, such as, for example, polyethylene sorbitanmonooleate. An aqueous suspension can also contain at least onepreservative, such as, for example, ethyl and n-propylp-hydroxybenzoate; at least one coloring agent; at least one flavoringagent; and/or at least one sweetening agent, including but not limitedto, for example, sucrose, saccharin, and aspartame.

Oily suspensions can, for example, be prepared by suspending at leastone compound of Formula (I) in either a vegetable oil, such as, forexample, arachis oil; olive oil; sesame oil; and coconut oil; or inmineral oil, such as, for example, liquid paraffin. An oily suspensioncan also contain at least one thickening agent, such as, for example,beeswax; hard paraffin; and cetyl alcohol. In order to provide apalatable oily suspension, at least one of the sweetening agents alreadydescribed hereinabove, and/or at least one flavoring agent can be addedto the oily suspension. An oily suspension can further contain at leastone preservative, including, but not limited to, for example, ananti-oxidant, such as, for example, butylated hydroxyanisol, andalpha-tocopherol.

Dispersible powders and granules can, for example, be prepared byadmixing at least one compound of Formula (I) with at least onedispersing and/or wetting agent; at least one suspending agent; and/orat least one preservative. Suitable dispersing agents, wetting agents,and suspending agents are as already described above. Exemplarypreservatives include, but are not limited to, for example,anti-oxidants, e.g., ascorbic acid. In addition, dispersible powders andgranules can also contain at least one excipient, including, but notlimited to, for example, sweetening agents; flavoring agents; andcoloring agents.

An emulsion of at least one compound of Formula (I) thereof can, forexample, be prepared as an oil-in-water emulsion. The oily phase of theemulsions comprising compounds of Formula (I) may be constituted fromknown ingredients in a known manner. The oil phase can be provided by,but is not limited to, for example, a vegetable oil, such as, forexample, olive oil and arachis oil; a mineral oil, such as, for example,liquid paraffin; and mixtures thereof. While the phase may comprisemerely an emulsifier, it may comprise a mixture of at least oneemulsifier with a fat or an oil or with both a fat and an oil. Suitableemulsifying agents include, but are not limited to, for example,naturally-occurring phosphatides, e.g., soy bean lecithin; esters orpartial esters derived from fatty acids and hexitol anhydrides, such as,for example, sorbitan monooleate; and condensation products of partialesters with ethylene oxide, such as, for example, polyoxyethylenesorbitan monooleate. Preferably, a hydrophilic emulsifier is includedtogether with a lipophilic emulsifier which acts as a stabilizer. It isalso preferred to include both an oil and a fat. Together, theemulsifier(s) with or without stabilizer(s) make-up the so-calledemulsifying wax, and the wax together with the oil and fat make up theso-called emulsifying ointment base which forms the oily dispersed phaseof the cream formulations. An emulsion can also contain a sweeteningagent, a flavoring agent, a preservative, and/or an antioxidant.Emulsifiers and emulsion stabilizers suitable for use in the formulationof the present invention include Tween 60, Span 80, cetostearyl alcohol,myristyl alcohol, glyceryl monostearate, sodium lauryl sulfate, glyceryldistearate alone or with a wax, or other materials well known in theart.

The compounds of Formula (I) can, for example, also be deliveredintravenously, subcutaneously, and/or intramuscularly via anypharmaceutically acceptable and suitable injectable form. Exemplaryinjectable forms include, but are not limited to, for example, sterileaqueous solutions comprising acceptable vehicles and solvents, such as,for example, water, Ringer's solution, and isotonic sodium chloridesolution; sterile oil-in-water microemulsions; and aqueous or oleaginoussuspensions.

Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules using one or more of the carriers or diluents mentioned for usein the formulations for oral administration or by using other suitabledispersing or wetting agents and suspending agents. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride, tragacanth gum, and/or various buffers. Other adjuvants andmodes of administration are well and widely known in the pharmaceuticalart. The active ingredient may also be administered by injection as acomposition with suitable carriers including saline, dextrose, or water,or with cyclodextrin (i.e. Captisol), cosolvent solubilization (i.e.propylene glycol) or micellar solubilization (i.e. Tween 80).

The sterile injectable preparation may also be a sterile injectablesolution or suspension in a non-toxic parenterally acceptable diluent orsolvent, for example as a solution in 1,3-butanediol. Among theacceptable vehicles and solvents that may be employed are water,Ringer's solution, and isotonic sodium chloride solution. In addition,sterile, fixed oils are conventionally employed as a solvent orsuspending medium. For this purpose any bland fixed oil may be employed,including synthetic mono- or diglycerides. In addition, fatty acids suchas oleic acid find use in the preparation of injectables.

A sterile injectable oil-in-water microemulsion can, for example, beprepared by 1) dissolving at least one compound of Formula (I) in anoily phase, such as, for example, a mixture of soybean oil and lecithin;2) combining the Formula (I) containing oil phase with a water andglycerol mixture; and 3) processing the combination to form amicroemulsion.

A sterile aqueous or oleaginous suspension can be prepared in accordancewith methods already known in the art. For example, a sterile aqueoussolution or suspension can be prepared with a non-toxicparenterally-acceptable diluent or solvent, such as, for example,1,3-butane diol; and a sterile oleaginous suspension can be preparedwith a sterile non-toxic acceptable solvent or suspending medium, suchas, for example, sterile fixed oils, e.g., synthetic mono- ordiglycerides; and fatty acids, such as, for example, oleic acid.

Pharmaceutically acceptable carriers, adjuvants, and vehicles that maybe used in the pharmaceutical compositions of this invention include,but are not limited to, ion exchangers, alumina, aluminum stearate,lecithin, self-emulsifying drug delivery systems (SEDDS) such asd-alpha-tocopherol polyethyleneglycol 1000 succinate, surfactants usedin pharmaceutical dosage forms such as Tweens, polyethoxylated castoroil such as CREMOPHOR surfactant (BASF), or other similar polymericdelivery matrices, serum proteins, such as human serum albumin, buffersubstances such as phosphates, glycine, sorbic acid, potassium sorbate,partial glyceride mixtures of saturated vegetable fatty acids, water,salts or electrolytes, such as protamine sulfate, disodium hydrogenphosphate, potassium hydrogen phosphate, sodium chloride, zinc salts,colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone,cellulose-based substances, polyethylene glycol, sodiumcarboxymethylcellulose, polyacrylates, waxes,polyethylene-polyoxypropylene-block polymers, polyethylene glycol andwool fat. Cyclodextrins such as alpha-, beta-, and gamma-cyclodextrin,or chemically modified derivatives such as hydroxyalkylcyclodextrins,including 2- and 3-hydroxypropyl-cyclodextrins, or other solubilizedderivatives may also be advantageously used to enhance delivery ofcompounds of the formulae described herein.

The pharmaceutically active compounds of this invention can be processedin accordance with conventional methods of pharmacy to produce medicinalagents for administration to patients, including humans and othermammals. The pharmaceutical compositions may be subjected toconventional pharmaceutical operations such as sterilization and/or maycontain conventional adjuvants, such as preservatives, stabilizers,wetting agents, emulsifiers, buffers etc. Tablets and pills canadditionally be prepared with enteric coatings. Such compositions mayalso comprise adjuvants, such as wetting, sweetening, flavoring, andperfuming agents.

The amounts of compounds that are administered and the dosage regimenfor treating a disease condition with the compounds and/or compositionsof this invention depends on a variety of factors, including the age,weight, sex, the medical condition of the subject, the type of disease,the severity of the disease, the route and frequency of administration,and the particular compound employed. Thus, the dosage regimen may varywidely, but can be determined routinely using standard methods. A dailydose of about 0.001 to 100 mg/kg body weight, preferably between about0.0025 and about 50 mg/kg body weight and most preferably between about0.005 to 10 mg/kg body weight, may be appropriate. The daily dose can beadministered in one to four doses per day. Other dosing schedulesinclude one dose per week and one dose per two day cycle.

For therapeutic purposes, the active compounds of this invention areordinarily combined with one or more adjuvants appropriate to theindicated route of administration. If administered orally, the compoundsmay be admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, magnesium oxide, sodium and calcium salts of phosphoric andsulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.

Pharmaceutical compositions of this invention comprise at least onecompound of Formula (I) and optionally an additional agent selected fromany pharmaceutically acceptable carrier, adjuvant, and vehicle.Alternate compositions of this invention comprise a compound of theFormula (I) described herein, or a prodrug thereof, and apharmaceutically acceptable carrier, adjuvant, or vehicle.

The present invention also encompasses an article of manufacture. Asused herein, article of manufacture is intended to include, but not belimited to, kits and packages. The article of manufacture of the presentinvention, comprises: (a) a first container; (b) a pharmaceuticalcomposition located within the first container, wherein the composition,comprises: a first therapeutic agent, comprising: a compound of thepresent invention or a pharmaceutically acceptable salt form thereof;and (c) a package insert stating that the pharmaceutical composition canbe used for the treatment of a cardiovascular and/or inflammatorydisorder (as defined previously). In another embodiment, the packageinsert states that the pharmaceutical composition can be used incombination (as defined previously) with a second therapeutic agent totreat cardiovascular and/or inflammatory disorder. The article ofmanufacture can further comprise: (d) a second container, whereincomponents (a) and (b) are located within the second container andcomponent (c) is located within or outside of the second container.Located within the first and second containers means that the respectivecontainer holds the item within its boundaries.

The first container is a receptacle used to hold a pharmaceuticalcomposition. This container can be for manufacturing, storing, shipping,and/or individual/bulk selling. First container is intended to cover abottle, jar, vial, flask, syringe, tube (e.g., for a cream preparation),or any other container used to manufacture, hold, store, or distribute apharmaceutical product.

The second container is one used to hold the first container and,optionally, the package insert. Examples of the second containerinclude, but are not limited to, boxes (e.g., cardboard or plastic),crates, cartons, bags (e.g., paper or plastic bags), pouches, and sacks.The package insert can be physically attached to the outside of thefirst container via tape, glue, staple, or another method of attachment,or it can rest inside the second container without any physical means ofattachment to the first container. Alternatively, the package insert islocated on the outside of the second container. When located on theoutside of the second container, it is preferable that the packageinsert is physically attached via tape, glue, staple, or another methodof attachment. Alternatively, it can be adjacent to or touching theoutside of the second container without being physically attached.

The package insert is a label, tag, marker, etc. that recitesinformation relating to the pharmaceutical composition located withinthe first container. The information recited will usually be determinedby the regulatory agency governing the area in which the article ofmanufacture is to be sold (e.g., the United States Food and DrugAdministration). In one embodiment, the package insert specificallyrecites the indications for which the pharmaceutical composition hasbeen approved. The package insert may be made of any material on which aperson can read information contained therein or thereon. For example,the package insert is a printable material (e.g., paper, plastic,cardboard, foil, adhesive-backed paper or plastic, etc.) on which thedesired information has been formed (e.g., printed or applied).

Methods of Preparation

The compounds of the present invention can be prepared in a number ofways well known to one skilled in the art of organic synthesis. Thecompounds of the present invention can be synthesized using the methodsdescribed below, together with synthetic methods known in the art ofsynthetic organic chemistry, or variations thereon as appreciated bythose skilled in the art. Preferred methods include, but are not limitedto, those described below. All references cited herein are herebyincorporated in their entirety by reference.

The compounds of this invention may be prepared using the reactions andtechniques described in this section. The reactions are performed insolvents appropriate to the reagents and materials employed and aresuitable for the transformations being effected. Also, in thedescription of the synthetic methods described below, it is to beunderstood that all proposed reaction conditions, including choice ofsolvent, reaction atmosphere, reaction temperature, duration of theexperiment and work up procedures, are chosen to be the conditionsstandard for that reaction, which should be readily recognized by oneskilled in the art. It is understood by one skilled in the art oforganic synthesis that the functionality present on various portions ofthe molecule must be compatible with the reagents and reactionsproposed. Such restrictions to the substituents that are compatible withthe reaction conditions will be readily apparent to one skilled in theart and alternate methods must then be used. This will sometimes requirea judgment to modify the order of the synthetic steps or to select oneparticular process scheme over another in order to obtain a desiredcompound of the invention. It will also be recognized that another majorconsideration in the planning of any synthetic route in this field isthe judicious choice of the protecting group used for protection of thereactive functional groups present in the compounds described in thisinvention. An authoritative account describing the many alternatives tothe trained practitioner is Greene and Wuts (Protective Groups InOrganic Synthesis, Third Edition, Wiley and Sons, 1999).

Compounds of Formula (I) may be prepared by reference to the methodsillustrated in the following Schemes. As shown therein the end productis a compound having the same structural formula as Formula (I). It willbe understood that any compound of Formula (I) may be produced by theschemes by the suitable selection of reagents with appropriatesubstitution. Solvents, temperatures, pressures, and other reactionconditions may readily be selected by one of ordinary skill in the art.Starting materials are commercially available or readily prepared by oneof ordinary skill in the art. Constituents of compounds are as definedherein or elsewhere in the specification.

As shown in Scheme 1, compounds of Formula (I) can be produced, startingwith the substituted 5-bromoindoles (2). 2 can be prepared from the3-formyl indoles (via reduction) or from the 3-H indoles, viaalkylation. Transition metal catalyzed cross coupling of 2 and boronate3 followed by olefin reduction and Boc deprotection affords 4, which canthen be coupled with pyridyl boronic acids and deprotected to give 6.Alkylation of 6 leads to the production of the compounds of Formula I.

In an alternative preparation, bromoindole 2b can first be coupled withboronate 3 and reduced. Chlorination proceeds selectively on the3-position, with bromination then providing the di-halogenated compound7.

EXAMPLES

Preparation of compounds of Formula (I), and intermediates used in thepreparation of compounds of Formula (I), can be prepared usingprocedures shown in the following Examples and related procedures. Themethods and conditions used in these examples, and the actual compoundsprepared in these Examples, are not meant to be limiting, but are meantto demonstrate how the compounds of Formula (I) can be prepared.Starting materials and reagents used in these examples, when notprepared by a procedure described herein, are generally eithercommercially available, or are reported in the chemical literature, ormay be prepared by using procedures described in the chemicalliterature.

Abbreviations

-   Ac acetyl-   AcOH acetic acid-   ACN acetonitrile-   AIBN 2,2-azobisiosbutyronitrile-   anhyd. anhydrous-   aq. aqueous-   BH3DMS boron dimethylsulfide-   Bn benzyl-   Bu butyl-   Boc tert-butoxycarbonyl-   CV Column Volumes-   DBU 1,8-diazabicyclo[5.4.0]undec-7-ene-   DCE dichloroethane-   DCM dichloromethane-   DEA diethylamine-   DIPEA diisopropylethylamine-   DMF dimethylformamide-   DMAP dimethylaminopyridine-   DMF-DMA N,N-dimethylformamide dimethyl acetal-   DMSO dimethylsulfoxide-   Et₃N triethylamine-   EtOAc ethyl acetate-   Et ethyl-   EtOH ethanol-   Et₂O diethyl ether-   H or H₂ hydrogen-   h, hr or hrs hour(s)-   HATU O-(7-azabenzotriazol-1-yl)-N, N, N′, N′-tetramethyluronium    hexafluorophosphate-   hex hexane-   i iso-   IPA isopropyl alcohol-   HOAc acetic acid-   HCl hydrochloric acid-   HPLC high pressure liquid chromatography-   LAH lithium aluminum hydride-   LC liquid chromatography-   LCMS Liquid Chromatograph-Mass Spectroscopy-   M molar-   mM millimolar-   Me methyl-   MeOH methanol-   MHz megahertz-   min. minute(s)-   mins minute(s)-   M⁺¹ (M+H)⁺-   MOM-Cl chloromethyl methyl ether-   MS mass spectrometry-   n or N normal-   NBS n-bromosuccinimide-   NIS N-iodosuccinimide-   nm nanometer-   nM nanomolar-   NMP N-methylpyrrolidine-   Pd/C palladium on carbon-   PdCl₂(dppf)    [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-   Pd₂(dba)₃ tris-(dibenzylideneacetone)dipalladium-   Pd(OAc)₂ palladium acetate-   Pet ether petroleum ether-   Ph phenyl-   Ret Time retention time-   sat. saturated-   TEA triethylamine-   TFA trifluoroacetic acid-   THF tetrahydrofuran-   TsCl 4-toluenesulfonyl chloride    2nd generation Xphos precatalyst:

(Chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)

Analytical and Preparative HPLC conditions:

Method QC-ACN-AA-XB: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mMammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mMammonium acetate; Temperature: 50° C.; Gradient: 0-100% B over 3minutes, then a 0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection:UV at 220 nm.

QC Method:

Method QC-ACN-TFA-XB: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm,1.7 μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1%trifluoroacetic acid; Temperature: 50° C.; Gradient: 0-100% B over 3minutes, then a 0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection:UV at 220 nm.

Method A1: L3 Acquity: Column: (LCMS) BEH C18, 2.1×50 mm, 1.7 μmparticles; Mobile Phase: (A) water; (B) acetonitrile; Buffer: 0.05% TFA;Gradient Range: 2%-98% B (0 to 1 min) 98% B (to 1.5 min) 98%-2% B (to1.6 min); Gradient Time: 1.6 min; Flow Rate: 0.8 mL/min; Analysis Time:2.2 min; Detection: Detector 1: UV at 254 nm; Detector 2: MS (ESI⁺).

Method B1: L2 Aquity (4); Column: (LCMS) BEH C18, 2.1×50 mm, 1.7 μmparticles; Mobile Phase: (A) water; (B) acetonitrile; Buffer: 0.05% TFA;Gradient Range: 2%-98% B (0 to 1 min) 98% B (to 1.5 min) 98%-2% B (to1.5 min); Gradient Time: 1.8 min; Flow Rate: 0.8 mL/min; Analysis Time:2.2 min; Detection: Detector 1: UV at 254 nm; Detector 2: MS (ESI⁺).

Method C1 SCP: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7 μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammoniumacetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammoniumacetate. Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a0.75-minute hold at 100% B; Flow: 1.11 mL/min; Detection: UV at 220 nm.

Method D1 SCP: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7 μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1%trifluoroacetic acid; Temperature: 50° C.; Gradient: 0-100% B over 3minutes, then a 0.75-minute hold at 100% B; Flow: 1.11 mL/min;Detection: UV at 220 nm.

Method E1 iPAC: Column: Waters Xbridge C18 4.6×50 mm 5 μm particles;Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate;Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate.Temperature: 50° C.; Gradient: 0-100% B over 1 minute; Flow: 4 mL/min;Detection: UV at 220 nm.

Method F1 iPAC: Column: Waters Acquity BEH C18 2.1×50 mm 1.7 μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1%trifluoroacetic acid; Temperature: 50° C.; Gradient: 0-100% B over 2.20minutes; Flow: 0.800 mL/min; Detection: UV at 220 nm.

(A): Column-Ascentis Express C18 (50×2.1 mm 2.7 μm) Mphase A: 10 mMNH₄COOH in water: ACN (98:02); Mphase B: 10 mM NH₄COOH in water: ACN(02:98), Gradient: 0-100% B over 3 minutes, Flow=1 mL/min.

(B): Waters Acquity BEH C18 (2.1×50 mm) 1.7 μm; Buffer: 5 mM ammoniumacetate pH 5 adjusted with HCOOH, Solvent A:Buffer:ACN (95:5), SolventB:Buffer:ACN (5:95), Method: % B: 0 min-5%:1.1 min −95%: 1.7 min-95%,Flow: 0.8 mL/min.

(C): Column-Ascentis Express C18 (50×2.1 mm 2.7 μm) Mobile phase A: 0.1%HCOOH in water; Mobile phase B: ACN. Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow rate: 1.0 mL/min.

(D): Kinetex XB-C18 (75×3 mm) 2.6 μm; Solvent A: 10 mM ammonium formatein water: acetonitrile (98:02); Mobile Phase B: 10 mM ammonium formatein water: acetonitrile (02:98); Temperature: 50° C.; Gradient: 0-100% Bover 3 minutes; Flow rate: 1.1 mL/min; Detection: UV at 220 nm.

(E): Column: Ascentis Express C18 (50×2.1) mm, 2.7 μm; Mobile Phase A:5:95 acetonitrile:water with 10 mM NH₄OAc; Mobile Phase B: 95:5acetonitrile:water with 10 mM NH₄OAc; Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow: 1.1 mL/min.

(F): Column: Ascentis Express C18(50×2.1) mm, 2.7 μm; Mobile Phase A:5:95 acetonitrile:water with 0.1% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.1% TFA; Temperature: 50° C.; Gradient: 0-100%B over 3 minutes; Flow: 1.1 mL/min.

(G): Column: Waters Acquity UPLC BEH C18 (2.1×50 mm), 1.7 μm; SolventA=100% water with 0.05% TFA; Solvent B=100% acetonitrile with 0.05% TFA;gradient=2-98% B over 1 minute, then a 0.5-minute hold at 98% B; Flowrate: 0.8 mL/min; Detection: UV at 220 nm.

(H): Column: Acentis Express C18 (50×2.1 mm) 1.7 m, Acentis C8 NH₄COOH 5min. M, Mobile Phase A: −10 mM ammonium formate: ACN (98:2), MobilePhase B: −10 mM ammonium formate: ACN (2:98), Flow: 1 mL/min.

(I) Column: Sunfire C18 (4.6×150) mm, 3.5 μm; Mobile Phase A: 5:95acetonitrile: water with 0.05% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.05% TFA; Temperature: 50° C.; Gradient:10-100% B over 12 minutes; Flow: 1 mL/min.

(J) Column: Sunfire C18 (4.6×150) mm, 3.5 μm; Mobile Phase A: 5:95acetonitrile:water with 0.05% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.05% TFA; Temperature: 50° C.; Gradient:10-100% B over 25 minutes; Flow: 1 mL/min.

(K): Column: Acquity UPLC BEH C18, 3.0×50 mm, 1.7 μm particles; MobilePhase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; MobilePhase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Method: %B: O min-20%: 1.1 min −90%:1.7 min-90%; Flow: 0.7 mL/min.

(L): Column: Kinetex XB-C18 (75×3 mm-2.6 μm), Mobile Phase A: 10 mMammonium formate: ACN (98:2), Mobile Phase B: 10 mM ammonium formate:ACN (2:98), Flow: 1 mL/min.

(M): Column: Acquity BEH C18 (3.0×50 mm) 1.7 μm, Mobile phase A: 0.1%TFA in water: Mobile phase B: 0.1% TFA in ACN, % B: 0 min −20%: 1.0 min−90%: 1.6 min 90%, Flow: 0.7 mL/min.

(N) Column: XBridge BEH XP C18 (50×2.1) mm, 2.5 μm; Mobile Phase A: 5:95acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5acetonitrile:water with 10 mM ammonium acetate; Temperature: 50° C.;Gradient: 0-100% B over 3 minutes, Flow: 1.1 mL/min; Detection: UV at220 nm.

Intermediates Intermediate T-1: tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

Intermediate T-1A: 5-bromo-3-isopropyl-1H-indole

A 250 mL round bottom flask was charged with triethylsilane (8.90 g, 77mmol), trichloroacetic acid (6.25 g, 38.3 mmol) and toluene (50 mL). Thesolution was heated to 70° C., then a solution of 5-bromo-1H-indole (5.0g, 25.5 mmol) and acetone (2.247 mL, 30.6 mmol) in toluene (30 mL) wasadded drop wise via an addition funnel. The resulting brown solution washeated at 70° C. for 1.5 h. The solution was cooled to 10° C., quenchedwith 10% sodium bicarbonate and diluted with diethyl ether. The organiclayer was separated, dried and concentrated under vacuum to afford crudecompound. The crude compound was purified using silica gelchromatography eluting with 5% ethyl acetate in hexanes to afford5-bromo-3-isopropyl-1H-indole (5.5 g, 23.10 mmol 95% yield) as an oil.LC retention time 1.42 min [D]. MS (E−) m/z: 238.2 (M+H).

Intermediate T-1B: tert-butyl4-(3-isopropyl-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate

To a mixture of 5-bromo-3-isopropyl-1H-indole (5.5 g, 23.10 mmol) andtert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate(7.50 g, 24.25 mmol) in a 250 mL round bottom flask were added THF (50mL) followed by an aqueous solution of potassium phosphate, dibasic(12.07 g, 69.3 mmol, 20 mL). The resulting reaction mixture was degassedfor 10 minutes with nitrogen gas, then PdCl₂(dppf)-CH₂Cl₂ adduct, (0.472g, 0.577 mmol) was added. The mixture was degassed again for 5 min. Theresulting reaction mixture was heated at 75° C. for 18 hours. Thereaction mixture was diluted with ethyl acetate (100 mL), poured into aseparate funnel and was washed with water (2×50 mL), brine (50 mL),dried over sodium sulfate, and concentrated to give crude product. Thecrude material was purified using silica gel chromatography, elutingwith 15% ethyl acetate in hexane. The fractions were collected andconcentrated to afford tert-butyl4-(3-isopropyl-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (6.5g, 83% yield) as an oil. LCMS retention time 1.21 min [B]. MS (E−) m/z:339 (M−H).

Intermediate T-1C: tert-butyl4-(3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

To a solution of tert-butyl4-(3-isopropyl-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (7.9g, 23.20 mmol) in ethyl acetate (150 mL) under a nitrogen atmosphere,was added palladium on carbon (0.617 g, 0.580 mmol). The vessel waspumped/purged three times with nitrogen gas and then evacuated. Hydrogengas was introduced via a balloon and the mixture was stirred at roomtemperature for 5 hours. The suspension was filtered through celite andthe filtrate was concentrated to give crude compound. The crude residuewas purified by silica gel chromatography, eluting with 15% ethylacetate in hexane. The combined fractions were collected andconcentrated to afford tert-butyl4-(3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (6.5 g, 82% yield)as a white solid. LCMS retention time 2.48 min [C]. MS (E−) m/z: 341(M−H).

Intermediate T-1

To a solution of tert-butyl4-(3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (6.3 g, 18.40mmol) in DCE (60 mL) was added NBS (3.27 g, 18.40 mmol) dissolved in DCE(50 mL) drop wise via an addition funnel over 10 min at 0° C. Theresulting brown solution was stirred at room temperature for 20 min. Thereaction was quenched with sodium sulfite solution (15 mL). Thevolatiles were removed. The residue was taken up in DCM (50 mL) and theaqueous layer was separated. The organic layer was dried over Na₂SO₄ andconcentrated to afford crude compound. The crude compound was purifiedby silica gel chromatography, the compound was eluted in 15% ethylacetate in Pet ether, the fractions was collected, and concentrated toafford tert-butyl 4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (6.4 g, 83% yield) as a white solid. LCMSretention time 2.58 min [H]. MS (E⁻) m/z: 367.2 (M−H). ¹H NMR (500 MHz,CHLOROFORM-d) δ 7.84 (br. s., 1H), 7.49 (d, J=0.9 Hz, 1H), 7.22 (d,J=8.4 Hz, 1H), 7.02 (dd, J=8.4, 1.5 Hz, 1H), 4.27 (br. s., 2H), 3.23(quin, J=7.1 Hz, 1H), 2.84 (br. s., 3H), 1.88 (d, J=13.1 Hz, 2H), 1.50(s, 9H), 1.43 (d, J=7.2 Hz, 6H), 1.24 (s, 2H).

Alternative Preparation of Intermediate T-1 Intermediate T-1A

A 5-liter 4-neck round bottom flask was charged with triethylsilane (489mL, 3061 mmol), trichloroacetic acid (250 g, 1530 mmol) and toluene (500mL). The solution was heated to 70° C. Next, 5-bromo-1H-indole (200 g,1020 mmol) dissolved in acetone (150 mL, 2040 mmol) and toluene (700 mL)was added dropwise over 30 minutes. After the addition was complete, theresulting solution was heated at 90° C. for 3 h. The reaction was thenquenched by adding 10% NaHCO₃ solution (˜2.5 liter) dropwise at 0-10° C.until the pH was basic. The organic layer and the aqueous layer wereseparated and the aqueous layer was extracted with MTBE (2×1000 mL). Thecombined organic layers were washed with water and brine solution, driedover Na₂SO₄ and concentrated under vacuum to get a brown color oil. Thecrude residue was purified by 750 g silica gel chromatography elutingwith PE:EtOAc (9:1). The product was eluted at 8% EtOAc in petroleumether, collected, and concentrated under vacuum at 50° C. A light browngummy liquid was obtained and hexane (100 mL) was added. The mixture wasstirred and cooled to −40° C. to −50 OC. After 10 min, a solid wasformed which was filtered and washed with a minimal amount cold hexane.The compound was dried under vacuum to afford5-bromo-3-isopropyl-1H-indole (215 g, 890 mmol, 87% yield) as anoff-white solid. LCMS MH⁺: 237.5; HPLC Ret. Time 3.75 min. Method D.

Intermediate T-1B

5-bromo-3-isopropyl-1H-indole (90 g, 378 mmol) and tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate(140 g, 454 mmol) was dissolved in THF (1200 mL) in a 2 L round-bottomedflask. Tripotassium phosphate (241 g, 1134 mmol) was dissolved in water(300 mL). The aqueous solution was added to the reaction mixture. Thereaction mixture was purged with N₂. Then PdCl₂(dppf)-CH₂Cl₂ adduct(7.72 g, 9.45 mmol) was added to the reaction mixture. The reactionmixture was again purged with N₂. The reaction mixture was stirred at80° C. for 18 h. The reaction mixture was filtered through celite andextracted with EtOAc. The combined organic layers were washed withbrine, dried (sodium sulfate), and concentrated to remove the solvent.The crude material was purified by silica gel chromatography. Theproduct was collected by eluting with 30% EtOAc:PE to afford tert-butyl4-(3-isopropyl-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (125g, 367 mmol). LCMS MH⁺: 341.2; HPLC Ret. Time 2.90 min.; Method: Column:Zorbax SB-18 (50×4.6 mm-5.0 μm); M. phase A: 10 mM NH₄COOH in H₂O:ACN(98:2); M. phase B: 10 mM NH₄COOH in H₂O:ACN (2:98); Flow rate: 1.5/min;Gradient: 30% B-100% B over 4 min. UV 220 nm.

Intermediate T-1C

In a 2 L round-bottomed flask,tert-butyl-4-(3-isopropyl-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate(125 g, 367 mmol) was dissolved in ethyl acetate (1200 mL). Pd/C (15.63g, 14.69 mmol) was added and the reaction mixture was degassed under N₂.The reaction mixture was stirred at room temperature for 18 h under H₂.Approximately 80% starting material was converted to product. Thereaction mass was filtered through celite and concentrated. The crudematerial was purified with silica gel chromatography. The product wascollected by eluting with 20% EtOAc:PE to afford tert-butyl4-(3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (105 g, 307 mmol,84% yield). LCMS MH⁺: 343.4; HPLC Ret. Time 2.61 min.; Method: Column:Zorbax SB-18 (50×4.6 mm-5.0 μm); M. phase A: 10 mM NH₄COOH in H₂O:ACN(98:2); M. phase B: 10 mM NH₄COOH in H₂O:ACN (2:98); Flow rate: 1.5/min;Gradient: 30% B-100% B over 4 min.; UV 220 nm.

Intermediate T-1

In a 2 L round-bottomed flask tert-butyl4-(3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (100 g, 292 mmol)was dissolved in 1,2-dichloroethane (1200 mL). NBS (52.0 g, 292 mmol)solution in 1,2-dichloroethane (400 mL) and THF (800 mL) was addeddropwise at 0° C. After the addition of NBS solution, the reactionmixture was stirred for 30 min. The reaction mass was quenched with 10%sodium thiosulfate solution at 0° C. and diluted with DCM. The combinedorganic layers were washed with brine, dried (sodium sulfate), andconcentrated. The crude material was purified with silica gelchromatography. The product was collected by eluting with 10% EtOAc:PE.The dibromo product was observed (approximately 5-10%). The material waswashed with cooled hexane to remove the dibromo product and affordtert-butyl 4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(87 g, 206 mmol, 70.7% yield). LCMS MH⁺—56: 365.0; HPLC Ret. Time 4.21min.; Method: Column: Kinetex XB-C18 (75×3 mm-2.6 μm); M. phase A: 10 mMNH₄COOH in H₂O:ACN (98:02); M. phase B: 10 mM NH₄COOH in H₂O:ACN(02:98); Flow rate: 1.0/min; Gradient: 20% B-100% B over 4 min. UV 220nm.

Intermediate T-2:tert-butyl-4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate

To a mixture of tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (1.0 g,2.373 mmol), 2-dicyclohexyphosphino-2′,6′-dimethoxybiphenyl (0.117 g,0.285 mmol), and bis(benzonitrile)palladium(II) chloride (0.027 g, 0.071mmol) in a 50 mL reaction tube was added dioxane (10 mL). The resultingreaction mixture was degassed for 10 min and then pinacolborane (0.456g, 3.56 mmol) was added followed by the dropwise addition of TEA (0.992mL, 7.12 mmol). The solution was again degassed for 5 min. The resultingreaction mixture was heated at 85° C. for 3 h. The reaction mixture wasconcentrated and the crude residue was dissolved in ethyl acetate (100mL), poured into a separatory funnel and washed thoroughly with water(2×250 mL). The organic layer was dried over Na₂SO₄ and filtered. Thefiltrate was concentrated under vacuum to afford the crude product. Theresidue was taken up in DCM (3 mL). The crude material was purified bycombiflash system by eluting with 12% EtOAc/Pet ether. Followingconcentration of the fractions, the product was isolated as a whitegummy product (0.75 g, 67.5% yield). LCMS retention time 4.27 min [H].MS (E−) m/z: 467.3 (M−H). ¹H NMR (400 MHz, CHLOROFORM-d) δ 8.35-8.12 (m,1H), 7.66-7.59 (m, 1H), 7.11-7.04 (m, 1H), 4.40-4.23 (m, 2H), 3.80-3.63(m, 1H), 2.99-2.67 (m, 3H), 1.98-1.84 (m, 2H), 1.79-1.64 (m, 2H),1.54-1.51 (m, 9H), 1.49-1.45 (m, 6H), 1.39-1.35 (m, 12H).

Alternative Preparation of Intermediate T-2

In a 1 L round-bottomed flask, tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl) piperidine-1-carboxylate (85 g,202 mmol) was dissolved in dioxane (850 mL). Next,2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (9.11 g, 22.19 mmol) andbis(benzonitrile) palladium chloride (3.87 g, 10.09 mmol) were added.Pinacolborane (387 g, 3026 mmol) was added followed by the addition ofTEA (84 mL, 605 mmol). The reaction reaction mixture was purged withnitrogen for 15-20 min. The reaction mixture was stirred at 90° C. for20 h. The reaction mixture was filtered through celite and the reactionwas quenched with brine solution. Effervescence was observed. Thereaction mixture was extracted with EtOAc, dried (sodium sulfate), andconcentrated. The crude material was purified with silica gelchromatography. The product was collected by eluting with 10% EtOAc:PEto afford tert-butyl4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate (62.5 g, 133 mmol, 66.1% yield). LCMS MH⁺:469.4. HPLC Ret. Time 3.04 min.; Method: Column: Zorbax SB-18 (50×4.6mm-5.0 μm); M. phase A: 10 mM NH₄COOH in H₂O:ACN (98:2); M. phase B: 10mM NH₄COOH in H₂O:ACN (2:98); Flow rate: 1.5/min; Gradient: 30% B-100% Bover 4 min.; UV 220 nm.

Intermediate T-3: Tert-butyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

To a mixture of tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (60 g, 142mmol), bis(benzonitrile)palladium(ii) chloride (1.639 g, 4.27 mmol),2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (3.51 g, 8.54 mmol) andanhydrous dioxane (407 ml) under N₂ at room temperature were addedpinacolborane (62.0 mL, 427 mmol) and triethylamine (59.5 mL, 427 mmol).The mixture was heated at 85° C. for 5 min. The starting material wasconsumed. After the reaction mixture was cooled to room temperature (awater ice bath was used to fasten the cooling), 2 mL of 2 M K₃PO₄solution was added. After the generation of bubbles diminished, theremainder of the 2 M potassium phosphate tribasic solution (214 mL, 427mmol) was added, followed by6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (29.9 g, 132 mmol)and PdCl₂(dppf)-CH₂Cl₂ adduct (4.07 g, 4.98 mmol). The reaction mixturewas heated at 85° C. for 2 h. The reaction went to completion. After themixture was cooled to room temperature, the organic layer (a suspension)and the aqueous layer was separated. The top organic layer was asuspension. It was concentrated and dissolved in DCM (1.5 L) to give adark DCM solution and aqueous layer on the top. The water was removedand the DCM extraction was dried over Na₂SO₄, filtered through a Celitepad, washed with DCM and concentrated to give 150 g crude wet mud. Thematerial was purified with silica gel chromatography using a Silica 40 gGold column. The column was eluted with DCM and ethyl acetate. Theproduct was collected when eluting with 50% ethyl acetate:DCM to affordtert-butyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(56.9 g, 117.0 mmol, 82% yield) as an off-white solid. LCMS MH⁺: 488.5.HPLC Ret. Time 1.13 min. Method G. ¹H NMR (499 MHz, CHLOROFORM-d) δ8.45-8.41 (m, 1H), 8.36-8.33 (m, 1H), 7.90-7.84 (m, 1H), 7.66-7.63 (m,1H), 7.39-7.34 (m, 1H), 7.17-7.12 (m, 1H), 4.39-4.26 (m, 2H), 3.04-2.94(m, 1H), 2.92-2.75 (m, 3H), 2.72-2.65 (m, 3H), 2.27-2.21 (m, 3H),2.00-1.90 (m, 2H), 1.83-1.71 (m, 2H), 1.54-1.51 (m, 9H), 1.42-1.38 (m,6H).

Intermediate T-4: Tert-butyl4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

To a mixture of tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (40 g, 95mmol), bis(benzonitrile)palladium(ii) chloride (1.092 g, 2.85 mmol),2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (2.338 g, 5.70 mmol) andanhydrous dioxane (271 mL) under N₂ at room temperature, were addedpinacolborane (41.3 mL, 285 mmol) and triethylamine (39.7 mL, 285 mmol).The mixture was heated at 85° C. for 10 min. The starting material wasconsumed. After the reaction mixture was cooled to room temperature, 2-5mL of 2 M K₃PO₄ aqueous solution was added. After bubbling slowed down,the remainder of the 2 M potassium phosphate tribasic solution (142 mL,285 mmol) was added, followed by6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (20 g, 88 mmol) andPdCl₂(dppf)-CH₂Cl₂ adduct (3.10 g, 3.80 mmol). The mixture was heated at70° C. for 1.5 h. After completion of the reaction, 81 g of crudeproduct after concentration was purified by silica gel chromatography (3kg Gold column) eluting with DCM and ethyl acetate. The product wascollected at 35% ethyl acetate:DCM to afford tert-butyl4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(52.6 g, 107 mmol, 113% yield). LCMS MH⁺: 490.1. HPLC Ret. Time 1.08min. Method G.

Intermediate F-1: 6-bromo-[1,2,4]triazolo[1,5-a]pyridine

Commercially available reagent: CAS No 356560-80-0

Intermediate F-2: 6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of 5-bromo-3-methylpyridin-2-amine (1.75 g, 9.36mmol) in N,N-dimethylformamide (13.04 mL, 168 mmol) was added DMF-DMA(12.53 mL, 94 mmol). The reaction mixture was heated to 130° C.overnight. After cooling to room temperature, the volatiles were removedunder reduced pressure to afford a brown oil. To an ice-cooled, stirredsolution of the crude product in methanol (100 mL) and pyridine (15 mL)was added hydroxylamine-O-sulfonic acid (1.587 g, 14.03 mmol). Thereaction mixture was allowed to warm to room temperature and was stirredovernight. The volatiles were removed under reduced pressure, and theresidue was partitioned between aqueous sodium bicarbonate solution andethyl acetate. The aqueous layer was further extracted with ethylacetate, and the combined organic layers were washed sequentially withwater (10 mL) and saturated aqueous brine solution (10 mL), dried overmagnesium sulfate, and concentrated in vacuo to afford6-bromo-8-methyl-[1,2,4]triazolo[1,5-a] pyridine (1.98 g). LC-MS:M+1=212/214. Rt=0.80 min, [A1]; ¹H NMR (400 MHz, DMSO-d₆) δ 9.20 (s,1H), 8.48 (s, 1H), 7.67 (s, 1H), 2.55 (s, 3H).

Intermediate F-3: 6-bromo-7-methyl-[1,2,4]triazolo[1,5-a]pyridine

To a 40 mL vial with a pressure relief septum were added5-bromo-4-methylpyridin-2-amine (5.00 g, 26.7 mmol), DMF (10 mL) andN,N-dimethylformamide dimethyl acetal (11.99 mL, 90 mmol). The vial washeated to 130° C. for 6 hours. The vial was cooled to room temperature,the volatiles were removed under vacuum. The resulting oil was dissolvedin MeOH (5 mL) and pyridine (3.24 mL, 40.1 mmol) and cooled to 0° C.Hydroxylamine-O-sulfonic acid (4.53 g, 40.1 mmol) was added over 15minutes and the mixture was allowed to warm to room temperatureovernight. The solution was concentrated under vacuum. The resultingwhite solid was partitioned between EtOAc and saturated sodiumbicarbonate. The organic layer was separated and the bicarbonate layerwas extracted with EtOAc (2×50 mL). The combined organics were washedwith water (50 mL) and brine (50 mL), dried over magnesium sulfate,filtered and concentrated to afford6-bromo-7-methyl-[1,2,4]triazolo[1,5-a] pyridine as a white solid. (4.5g, 21.22 mmol, 79% yield). LC-MS: M+1=212/214, rt=0.70 min., [A1].

Intermediate F-4: 6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine

To a 40 mL vial with a pressure relief septum were added5-bromo-3,4-dimethylpyridin-2-amine (5.00 g, 24.87 mmol), DMF (10 mL)and N,N-dimethylformamide dimethyl acetal (11.15 mL, 83 mmol). The vialwas heated to 80° C. for 6 hours. The vial was cooled to roomtemperature. The volatiles were removed under vacuum and the resultingoil was dissolved in MeOH (5 mL) and pyridine (3.02 mL, 37.3 mmol) andcooled to 0° C. Hydroxylamine-O-sulfonic acid (4.22 g, 37.3 mmol) wasadded over 15 minutes and the mixture allowed to warm to roomtemperature overnight. The solution was concentrated under vacuum. Theresulting white solid was partitioned between EtOAc and 1.5 M potassiumphosphate solution. The organic layer was separated and the aqueouslayer was extracted with EtOAc (2×50 mL). The combined organics werewashed with water (50 mL) and brine (50 mL), dried over magnesiumsulfate, filtered and concentrated to give a white solid. The solid wasdissolved in DCM and MeOH and charged to an 80 G silica gel column whichwas eluted with 0-100% ethyl acetate/hexane. Following concentration ofthe fractions, 6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (5.2g, 23.00 mmol, 92% yield) was collected as a whitish solid. LC-MS:M+1=226/228, rt=0.75 min, [A1]; ¹H NMR: ¹H NMR (400 MHz, CHLOROFORM-d) δ8.68 (s, 1H), 8.26 (s, 1H), 2.68 (s, 3H), 2.50 (s, 3H).

Alternative Preparation of Intermediate F-4

To the suspension of 5-bromo-3,4-dimethylpyridin-2-amine (10 g, 49.7mmol) in DMF (50 mL) was added 1,1-dimethoxy-N,N-dimethylmethanamine(15.32 mL, 114 mmol). The mixture was stirred at 110° C. for 12 h underN₂. All the starting material amine was converted to intermediate imine(M+1, 256) after 12 h. The reaction mixture was concentrated to removevolatiles under high vacuum rotavap. Solvent DMF still remained in theblack reaction mixture. The resulting residue was diluted with MeOH (50mL) and pyridine (6.03 mL, 74.6 mmol). The mixture was cooled to 0° C.and hydroxylamine-O-sulfonic acid (8.88 g, 74.6 mmol) was added over 15min. The mixture was stirred at room temperature over 24 h. The reactionwas completed and the desired product was found after 19 h. The crudereaction mixture was concentrated to remove volatiles. The resultingyellow solid was dissolved in 200 mL EtOAc and quenched with saturatedNaHCO₃ solution slowly (200 mL) with gas generated during the additionof sodium bicarbonate. The organic layer was separated and the aqueouslayer was back-extracted with EtOAc. The combined organic layer waswashed with H₂O (30 mL), brine (2×30 mL) and dried over Na₂SO₄. Thecrude product was purified with silica gel chromatography eluting withEtOAc and hexane to afford6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (8 g, 35.4 mmol,71.1% yield). LCMS MH⁺: 226.08. HPLC Ret. Time 0.71 min. Method G. ¹HNMR (400 MHz, CHLOROFORM-d) δ 8.79-8.63 (m, 1H), 8.39-8.10 (m, 1H),2.81-2.61 (m, 3H), 2.57-2.48 (m, 3H).

Intermediate F-5: 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of 5-bromo-3-methoxypyridin-2-amine (7.5 g, 36.9mmol) in DMF (15 mL) was added DMF-DMA (15 mL, 112 mmol). The reactionmixture was heated to 130° C. overnight. After cooling to roomtemperature, the volatiles were removed under reduced pressure toprovide a brown oil. To an ice-cooled, stirred solution of the brown oilin methanol (150 mL) and pyridine (20 mL) was addedhydroxylamine-O-sulfonic acid (6.27 g, 55.4 mmol). The reaction mixturewas allowed to warm to room temperature and was stirred overnight. Thevolatiles were removed under reduced pressure, and the residue waspartitioned between aqueous sodium bicarbonate solution and ethylacetate. The aqueous layer was further extracted with ethyl acetate, andthe combined organic layers were washed sequentially with water (10 mL)and saturated aqueous brine solution (10 mL), dried over sodium sulfate,and concentrated in vacuo to afford crude product. The residue was takenup in DCM (3 mL). The crude was purified by combiflash 3% MeOH: 97%CHCl₃. Following concentration of fractions,6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (5.0 g, 21.93 mmol,59.4% yield) was collected as a yellow solid. LCMS: M⁺¹=228.5,R_(t)=1.06 min., Column: ZORBAX SB C18 (50×4.6 mm, 5.0 μM) Method: 10 mMNH₄COOH in water+ACN; ¹H NMR (400 MHz, DMSO-d₆) δ=4.01 (s, 3H), 7.26 (s,1H), 8.45 (s, 1H), 8.95 (s, 1H).

Intermediate F-6:6-bromo-8-(methoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine

To a 40 mL reaction vial, were added6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (2.000 g, 9.43 mmol),AIBN (0.155 g, 0.943 mmol), NBS (1.679 g, 9.43 mmol), and CCl₄ (15 mL).The vial was sealed and heated to 75° C. overnight. The reaction mixturewas cooled to room temperature and concentrated to dryness. The residuewas used without purification in the subsequent step.

To a 40 mL vial, were added the above residue, THF (15 mL), MeOH (10mL), and aqueous NaOH (28.3 mL, 28.3 mmol). The reaction vial was cappedand heated to 75° C. for 1 hour. LC-MS showed clean conversion to theproduct. Water and ethyl acetate was added and the layers wereseparated. The organics were washed with water, then brine, dried overNa₂SO₄, filtered, and concentrated to give an off-white solid. LC-MS:M+1=242, rt=1.31 min, [A1]. ¹H NMR (400 MHz, DMSO-d₆) δ 9.41-9.28 (m,1H), 8.52 (s, 1H), 7.78-7.65 (m, 1H), 4.84-4.70 (m, 2H), 3.42 (s, 3H).

Intermediate F-7: 6-2-(2-amino-5-bromo-1,2-dihydropyridin-3-yl)ethanol

In a 100 mL 2-neck round bottom flask, and under a nitrogen atmosphere,was added 2-(2-aminopyridin-3-yl)acetic acid (0.250 g, 1.622 mmol) andTHF (8 mL). At 5° C., LAH was added portion-wise to the solution. Theice bath was removed and the reaction mixture was heated at refluxovernight. After 16 hours, the solvent had evaporated. Diethyl ether wasadded. Following cooling, the reaction mixture was placed in an icebath. The LAH was quenched with MeOH, then water. Sodium sulfate wasadded and the mixture was filtered, and washed with diethyl ether. Thefiltrate was concentrated and then dissolved in DCM (5 mL) and cooled to5° C. Next, NBS (0.289 g, 1.622 mmol) in DCM (2 mL) was added. Thereaction mixture was warmed to room temperature. The reaction wasquenched with 2 mL of a 10% sodium sulfite solution. DCM (20 mL) andwater (20 mL) were added and the contents was added to a separatoryfunnel. The layers were separated. The organics were washed with brinedried over Na₂SO₄, filtered and concentrated to give crude product.LC-MS: M⁺¹=219, R_(t)=0.49 min, [A1]. This material was carried onsimilarly as in general procedure for F-2 to afford(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethanol (0.065 g, 73%).LC-MS: M⁺¹=242/244, R_(t)=0.65 min, [A1].

Intermediate F-8: (6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol

Intermediate F-8 was prepared according to general procedure for F-6starting from 6-bromo-8-methyl-[1,2,4]triazolo[1,5-a] pyridine andwithout methanol in the second step. LC-MS: M⁺¹=228/230, R_(t)=0.60 min,[A1].

Intermediate F-9:rac-1-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol

In a 40 mL reaction vial were added 2-amino-5-bromonicotinaldehyde(0.750 g, 3.73 mmol) and under nitrogen gas, THF (10 mL). The mixturewas cooled to −20° C. and 3 M methylmagnesium chloride in Et20 (4.97 mL,14.92 mmol) was added via syringe over 20 minutes. The reaction mixturewas warmed to room temperature and stirred for 3 hours. The reactionmixture was cooled to −20° C. and quenched slowly with saturatedammonium chloride. Water and ethyl acetate were added and the layerswere separated. The collected organics were washed with saturated NaCl,dried over Na₂SO₄, filtered and concentrated to dryness to affordrac-1-(2-amino-5-bromopyridin-3-yl)ethanol. This material was carried onsimilarly as in general procedure for F-1 to affordrac-1-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)ethan-1-ol (0.53 g,58%). LC-MS: M⁺¹=242/244, R_(t)=0.58 min, [A1].

Intermediate F-10:2-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol

In a 40 mL reaction vial was added methyl 2-amino-5-bromonicotinate(1.240 g, 5.37 mmol) and under a nitrogen atmosphere, THF (10.73 mL).The mixture was cooled to −20° C. and 3 M methylmagnesium chloride inEt₂O (7.16 mL, 21.47 mmol) was added via syringe over 20 minutes. Thereaction mixture was warmed to room temperature and stirred for 3 hours.The reaction mixture was cooled to −20° C. and the reaction was quenchedslowly with the addition of saturated ammonium chloride. Water and ethylacetate were added and the layers were separated. The collected organicswere washed with saturated NaCl, dried over Na₂SO₄, filtered andconcentrated to dryness to afford 2-(2-amino-5-bromopyridin-3-yl)propan-2-ol LC-MS: M⁺¹=231.3/233.0, R_(t)=0.49 min, [A1]. This materialwas carried on similarly as in general procedure for F-1 to afford2-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)propan-2-ol (0.65 g, 59%).LC-MS: M⁺¹=255.6/257.8, R_(t)=0.85 min, [D1].

Intermediate F-11:(6-bromo-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol

Intermediate F-11A: (2-amino-4-methylpyridin-3-yl)methanol

In a 100 mL Schlenk flask (heat gun dried) was addedN-(4-methylpyridin-2-yl) pivalamide (0.300 g, 1.560 mmol). Diethyl ether(5.20 mL) was added and the reaction mixture was cooled to −78° C. Next,1.7 M tert-butyllithium in pentane (2.019 mL, 3.43 mmol) was added viasyringe, drop-wise. The reaction mixture was stirred at −78° C. for 3hours and then chloromethyl methyl ether (0.142 mL, 1.872 mmol) wasintroduced. The reaction mixture was warmed to room temperature andstirred overnight. The reaction was quenched with water. Ethyl acetatewas added to the mixture. The mixture was poured into a separatoryfunnel and the layers were separated. The organics were washed withwater, then brine, dried over Na₂SO₄, filtered and concentrated. Thecrude oil was purified on a silica gel using 0-50% ethyl acetate/hexane.Following concentration of the fractions,N-(3-(methoxymethyl)-4-methylpyridin-2-yl)pivalamide was collected as atan oil. This material was suspended in 4 M aqueous HCl and heated to110° C. for 48 hours. The reaction mixture was cooled to roomtemperature, diluted with diethyl ether and the contents poured into aseparatory funnel. The layers were separated and the organic layer wasdiscarded. The aqueous layer was basified with 1.5 M potassium phosphatedibasic solution and the suspension was extracted with ethyl acetate(three times extracted). The combined organics were washed with brine,dried over Na₂SO₄, filtered and concentrated to afford(2-amino-4-methylpyridin-3-yl)methanol (0.1 g, 46%). LC-MS: (M⁺¹) notobserved on instrument, R_(t)=0.39 min by UV only, [A1].

Intermediate F-11B: (2-amino-5-bromo-4-methylpyridin-3-yl)methanol

In a 40 mL reaction vial was added(2-amino-4-methylpyridin-3-yl)methanol (0.200 g, 1.448 mmol), DCM, andNBS (0.258 g, 1.448 mmol) as a suspension in 5 mL of DCM. The reactionmixture was stirred for 15 minutes. The reaction was quenched with a 10%sodium sulfite solution (1 mL). The reaction mixture was diluted withwater and DCM, and transferred to a separatory funnel. The layers wereseparated and the organics were washed with brine, dried over Na₂SO₄,filtered and concentrated to afford(2-amino-5-bromo-4-methylpyridin-3-yl)methanol (0.08 g, 26%). LC-MS:M⁺¹=217/219, R_(t)=0.45 min, [A1].

Intermediate F-11

Intermediate F-11 was prepared from Intermediate F-11B according to thegeneral procedure for F-2 to afford(6-bromo-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)methanol LC-MS:M⁺¹=242/244, R_(t)=0.60 min, [A1].

Intermediate F-12:6-bromo-8-(methoxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine

Intermediate F-12A:6-bromo-8-(methoxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine

In a 40 mL reaction vial were addedN-(3-(methoxymethyl)-4-methylpyridin-2-yl) pivalamide (0.100 g, 0.423mmol) and 6 N aqueous HCl (2.116 mL, 2.116 mmol). The vial was cappedand heated to 80° C. overnight. The mixture was basified with a 1.5 Mdibasic potassium phosphate solution. The aqueous layer was extractedwith ethyl acetate (2×50 mL). The combined organics were washed with asaturated NaCl solution, dried over Na₂SO₄, filtered and concentrated toafford 3-(methoxymethyl)-4-methylpyridin-2-amine (R_(t)=0.44 min.) [A1].This material was suspended in DCM (4 mL). NBS (0.075 g, 0.423 mmol) wasdissolved in 1 mL of DCM and added to the reaction mixture drop-wise viaa pipet over 5 minutes. The reaction was quenched with the addition of 1mL of a 10% sodium sulfite solution. The organic layer was pipetted offand concentrated. The residue was purified on silica gel using 0-10%MeOH/DCM. Following concentration of the fractions,5-bromo-3-(methoxymethyl)-4-methylpyridin-2-amine was collected as a tanoil. LC-MS: M⁺¹=231/233, R_(t)=0.53 min. 0.60 min, [D1].

Intermediate F-12

Intermediate F-12 was prepared from Intermediate F-12A according to thegeneral procedure for F-1 to afford6-bromo-8-(methoxymethyl)-7-methyl-[1,2,4]triazolo[1,5-a] pyridine (0.03g, 30%). LC-MS: M⁺¹=256/258, R_(t)=1.07 min. 0.60 min, [A1].

Intermediate F-13:2-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)acetonitrile

To a 40 mL reaction vial was added(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl) methanol (0.500 g, 2.193mmol) followed by the slow addition of SOCl₂ (1.600 mL, 21.93 mmol). Thereaction mixture was stirred at 50° C. overnight. The reaction mixturewas concentrated and placed under vacuum to remove the excess thionylchloride. Next, acetonitrile, water and KCN (0.714 g, 10.96 mmol) inwater (1 mL) were added. The reaction vessel was sealed and heated to50° C. overnight. The reaction mixture was diluted with 1.5 M dibasicpotassium phosphate solution and ethyl acetate was added. The reactionmixture was poured into a separatory funnel and the layers wereseparated. The organics were washed with brine, then dried over Na₂SO₄,filtered and concentrated to afford 2-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)acetonitrile as a tan solid (0.21 g, 40%).LC-MS: M⁺¹=236/238, R_(t)=0.60 min, [A1].

Intermediate F-14:6-bromo-8-fluoro-7-methyl-[1,2,4]triazolo[1,5-a]pyridine

In a 40 mL reaction vial was added 3-fluoro-4-methylpyridin-2-amine(0.250 g, 1.982 mmol) in DCM (5 mL). To this was added a suspension ofNBS (0.353 g, 1.982 mmol) in DCM (2 mL). The reaction mixture wasstirred for 30 minutes. The reaction was quenched with the addition of 5mL of a 10% sodium sulfite solution. DCM and water were added and thereaction mixture was poured into a separatory funnel. The layers wereseparated. The collected organics were washed with brine, dried overNa₂SO₄, filtered and concentrated to afford5-bromo-3-fluoro-4-methylpyridin-2-amine. This material was carried onsimilarly as in general procedure for F-2 to afford6-bromo-8-fluoro-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (0.45 g, 49%).LC-MS: M⁺¹=230/232, R_(t)=0.71 min. 0.60 min, [A1].

Intermediate F-15: (6-bromo-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol

Intermediate F-15A:6-bromo-7-(bromomethyl)-[1,2,4]triazolo[1,5-a]pyridine

In a 40 mL reaction vial were added6-bromo-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (0.670 g, 3.16 mmol),carbon tetrachloride (6.32 mL), NBS (0.562 g, 3.16 mmol) and AIBN (0.052g, 0.316 mmol). The reaction vial was capped and heated at 75° C. for 5hours. The reaction mixture was cooled to room temperature, filtered andthe precipitate was washed with CCl₄. The filtrate was concentrated toafford 6-bromo-7-(bromomethyl)-[1,2,4]triazolo [1,5-a]pyridine as alight yellow residue (0.72 g, 78%). LC-MS: M⁺¹=290/292/294, R_(t)=0.75min., [A1].

Intermediate F-15

To a 40 mL vial were added6-bromo-7-(bromomethyl)-[1,2,4]triazolo[1,5-a]pyridine (1.000 g, 3.44mmol), acetone (11 mL), sodium iodide (0.515 g, 3.44 mmol) and potassiumacetate (0.675 g, 6.87 mmol). The reaction mixture was capped and heatedto 55° C. for 17 hours. The volatiles were removed under a stream ofnitrogen gas and to the residue were added THF (10 mL), 1 mL of water,and sodium hydroxide (2.58 mL, 10.31 mmol). The vial was capped andheated at 65° C. for 8 hours. The mixture was treated with 1 N HCl toapproximately pH 7. Ethyl acetate was added and the layers wereseparated. The organics were washed with brine, dried over Na₂SO₄,filtered and concentrated to afford(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methanol as a whitish solid(0.35 g, 44%). LC-MS: M⁺¹=228/230, R_(t)=0.54 min., [A1].

Intermediate F-16:2-((6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethyl acetate

Intermediate F-16A: 2-((2-amino-5-bromopyridin-3-yl)oxy)ethyl acetate

In a 40 mL reaction vial under nitrogen gas, was added2-amino-5-bromopyridin-3-ol (0.320 g, 1.693 mmol) and DMF (5 mL). Themixture was cooled to 5° C. and NaH (0.102 g, 2.54 mmol) was added. Thereaction mixture was stirred at 5° C. for 1 hour. Next, 2-bromoethylacetate (0.283 mL, 2.54 mmol) was introduced neat via a syringe. Thereaction mixture was stirred at 5° C. and slowly warmed to roomtemperature overnight. The mixture was cooled to 5° C. and carefullydiluted with water. Ethyl acetate was added and the mixture wastransferred to a separatory funnel. The layers were separated and theorganics were washed with brine, dried over sodium sulfate, filtered andconcentrated to afford 2-((2-amino-5-bromopyridin-3-yl)oxy)ethyl acetateas a tan oil (0.45 g, 97%). LC-MS: M⁺¹=275/277, rt=0.52 min, [A1].

Intermediate F-16

Intermediate F-16A carried on similarly to general procedure for F-1 toafford 2-((6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)oxy)ethyl acetateas a tan solid. LC-MS: M⁺¹=300/302, R_(t)=0.69 min, [A1].

Intermediate F-17:6-bromo-8-(ethoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine

Intermediate F-17A: 6-bromo-8-(bromomethyl)-[1,2,4]triazolo[1,5-a]pyridine

To a 40 mL reaction vial were added6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (2.000 g, 9.43 mmol),AIBN (0.155 g, 0.943 mmol), NBS (1.679 g, 9.43 mmol), and CCl₄ (15 mL).The vial was sealed and heated to 75° C. overnight. The reaction mixturewas cooled to room temperature, filtered and the precipitate was washedwith CCl₄. The filtrate was concentrated to dryness to afford6-bromo-8-(bromomethyl)-[1,2,4]triazolo[1,5-a] pyridine, as a lightyellow residue (1.9 g, 69%). LC-MS: M⁺¹=290/292/294, R_(t)=0.73 min.,[A1].

Intermediate F-17

To a 40 mL reaction vial were added6-bromo-8-(bromomethyl)-[1,2,4]triazolo[1,5-a] pyridine (0.300 g, 1.031mmol), ethanol (3.44 mL), sodium iodide (0.015 g, 0.103 mmol) andpotassium acetate (0.051 g, 0.516 mmol). The reaction vial was cappedand heated to 55° C. overnight. The reaction mixture was cooled to roomtemperature and concentrated to dryness. Water and ethyl acetate wereadded and the mixture was transferred to a separatory funnel. The layerswere separated and the organics were washed with water, then brine,dried over Na₂SO₄, filtered, and concentrated to afford6-bromo-8-(ethoxymethyl)-[1,2,4]triazolo[1,5-a]pyridine (0.2 g, 72%).LC-MS: M⁺¹=256/258, R_(t)=0.79 min, [A1].

The following Fragments were prepared in a fashion similar to thesynthetic methods described above.

TABLE 1 Interm. LCMS Ret HPLC No. Starting Material Structure MH⁺ TimeMethod F-18 5-bromo-3,6-dimethyl- pyridin-2-amine

226/228 0.77 [TS1] F-19 2-amino-5- bromonicotinonitrile

222.9 0.60 [TS1] F-20 5-bromo-3- fluoropyridin-2-amine

216/218 0.62 [A1] F-21 5-bromo-4-methyl pyridin-2-amine

212/214 1.40 D F-22 5-bromo-6-methyl pyridin-2-amine

212/214 1.47 D F-23 5-bromo-3-methyl pyridin-2-amine

226/228 1.46 D F-24 5-bromo-4-methyl- pyridin-2-amine

226/228 1.45 D F-25 5-bromo-3-fluoro- pyridin-2-amine

230/232 1.22 D F-26 5-bromo-4-fluoro- pyridin-2-amine

230/232 1.12 D F-27 5-bromo-3-(trifluoro- methyl)pyridin-2- amine

266/268 1.73 D F-28 5-bromo-4-methoxy- pyridin-2-amine

228/230 1.39 D F-29 5-bromo-3-ethoxy- pyridin-2-amine

242/244 0.99 D F-30 5-bromo-3-ethoxy- pyridin-2-amine

256/258 1.93 D F-31 5-bromo-3-methoxy- pyridin-2-amine

242/244 1.55 D F-32 5-bromo-3-(difluoro- methoxy)pyridin-2- amine

278/280 2.06 D F-33 5-bromo-4-isobutoxy- pyridin-2-amine

270/272 2.06 D F-34 5-bromo-3-chloro- 4-methylpyridin- 2-amine

260/262 1.41 B F-35 3,5-dibromo-4-methyl- pyridin-2-amine

242/244 1.1 B F-36 5-bromo-3-chloro-4- methylpyridin-2-amine

246/248 9.9 A F-37 5-bromo-6-methyl pyridin-2-amine

226/228 0.55 A F-38 5-bromo-3-chloro- pyridin-2-amine

246/248 0.55 A F-39 5-bromo-3-chloro- pyridin-2-amine

232/234 0.48 A F-40 5-bromo-4-(trifluoromethyl) pyridin-2-amine

280/282 0.67 K

Intermediate F-41:4-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine

Intermediate F-41A: 5-bromo-3-iopyridin-2-amine

To a stirred solution of 5-bromopyridin-2-amine (4.0 g, 23.12 mmol), TFA(2.316 mL, 30.1 mmol) in DMF (100 mL) at 0° C. were added portion wiseNIS (6.76 g, 30.1 mmol). The reaction mixture was stirred at 50° C. for16 h. The reaction mixture was quenched with ice cold water and sodiumthiosulphate solution (3:1), the product was precipitated by adding thesaturated NaHCO₃ solution (adjust pH-8), stirred for 10 min at 0° C. Theresulting solid compound was collected by filtration to afford5-bromo-3-iodopyridin-2-amine (5.1 g, 17.06 mmol, 73.8% yield) as abrown solid. MS (E⁺) m/z: 298.9 (M). Retention time: 1.16 min. [K].

Intermediate F-42B: (E)-N′-(5-bromo-3-iodopyridin-2-yl)-N,N-dimethylformimidamide

A solution of DMF-DMA (11.42 mL, 85 mmol) and5-bromo-3-iodopyridin-2-amine (5.1 g, 17.06 mmol) in DMF (20.0 mL) wasstirred at 130° C. for 16 h. The reaction mixture was cooled to roomtemperature and the volatiles were evaporated. The mixture was dried inhigh vacuum to afford(E)-N′-(5-bromo-3-iodopyridin-2-yl)-N,N-dimethylformimidamide (6.2 g,17.51 mmol, 103% yield) as a brown semi-solid. MS (E⁺) m/z: 355.8(M+2H). Retention time: 1.51 min. [K].

Intermediate F-43C: 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of(E)-N′-(5-bromo-3-iodopyridin-2-yl)-N,N-dimethylformimidamide (6.1 g,17.23 mmol) and pyridine (6.97 mL, 86 mmol) in MeOH (80.0 mL) at 0° C.was added hydroxylamine-O-sulfonic acid (3.89 g, 34.5 mmol). Thereaction mixture was stirred at room temperature for 16 h. The reactionmixture was quenched with ice cold water and volatiles were evaporated.The mixture was dried in high vacuum. The residue was dissolved insaturated NaHCO₃ solution and extracted with chloroform (2×200 mL) andwashed with brine. The organic layer was dried over sodium sulphate andconcentrated. The resulting material was purified by silica gelchromatography. The compound was eluted with 65% ethyl acetate andpetroleum ether to afford 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine(1.8 g, 5.56 mmol, 32.2% yield) as a light yellow solid. MS (E⁺) m/z:325.8, Retention time: 1.577 min. [L].

Intermediate F-43

A stirred mixture of 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine(0.300 g, 0.926 mmol), morpholine (0.403 g, 4.63 mmol), and Cs₂CO₃(0.905 g, 2.78 mmol) in DMF (10.0 mL) was degassed for 5 min. Next,Pd₂(dba)₃ (0.085 g, 0.093 mmol) and Xantphos (0.054 g, 0.093 mmol) wereadded. The reaction mixture was stirred at 120° C. for 2.5 h in amicrowave system. The reaction mixture was diluted with ethyl acetate,filtered and washed with excess ethyl acetate. The combined organiclayers were washed with water, brine, dried over sodium sulphate andevaporated to afford crude material. The crude material was purifiedusing a 24 g silica gel column, compound was eluted with 35% ethylacetate and petroleum ether to afford4-(6-bromo-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine (0.180 g, 0.636mmol, 68.6% yield) as a light yellow solid. MS (E⁺) m/z: 285.0, R_(t):1.60 min. [L].

The following examples were prepared according to the general proceduredescribed above for Intermediate F-43.

TABLE 2 Interme- LCMS diate [M + R_(t) HPLC No. Structure 2H] (min)Method F-44

298.0 0.78 K F-45

243.0 1.05 K F-46

297.0 1.06 K F-47

287.0 0.90 K F-48

319.0 0.76 K F-49

333.0 0.75 K F-50

271.0 0.79 K F-51

305.8 1.350 K

Intermediate F-52: 6-bromo-8-cyclopropyl-[1,2,4] triazolo[1,5-a]pyridine

A solution of 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine (0.400 g,1.235 mmol) and cyclopropylboronic acid (0.318 g, 3.70 mmol) in amixture of toluene (10.0 mL) and water (2.0 mL) was degassed for 5 min.Next, tricyclohexylphosphine (0.069 g, 0.247 mmol), Pd(OAc)₂ (0.028 g,0.123 mmol) and Na₂CO₃ (1.852 mL, 3.70 mmol) were added. The resultantreaction mixture was stirred at 100° C. for 14 h in a sealed tube. Thereaction mixture was cooled to room temperature, diluted with ethylacetate, filtered, and washed with excess ethyl acetate. The combinedorganic layers were washed with water, brine, dried over sodiumsulphate, and evaporated to afford the crude compound. The crudecompound was purified using a 40 g silica column. The compound waseluted with 35% ethyl acetate and pet ether to afford6-bromo-8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridine (0.240 g, 1.008mmol, 82% yield) as a light yellow solid. MS (E⁺) m/z: 240.0, R_(t):1.05 min. [M].

Intermediate F-53:4-(6-bromo-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine

Intermediate F-53A:(E)-N′-(5-bromo-3-iodopyridin-2-yl)-N,N-dimethylacetimidamide

A solution of 1,1-dimethoxy-N,N-dimethylpropan-2-amine (24.63 g, 167mmol) and 5-bromo-3-iodopyridin-2-amine (5.0 g, 16.73 mmol) in DMF (20.0mL) was stirred at 130° C. for 16 h. The reaction mixture was cooled toroom temperature. The volatiles were evaporated and the material wasdried in high vacuum to afford(E)-N′-(5-bromo-3-iodopyridin-2-yl)-N,N-dimethylacetimidamide (5.8 g,15.76 mmol, 94% yield) as a brown semi-solid. MS (E⁺) m/z: 370.0, R_(t):0.68 min. [M].

Intermediate F-53B:6-bromo-8-iodo-2-methyl-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of(E)-N′-(5-bromo-3-iodopyridin-2-yl)-N,N-dimethylacetimidamide (4.5 g,12.23 mmol) and pyridine (4.94 mL, 61.1 mmol) in methanol (80.0 mL) at0° C. was added hydroxylamine-O-sulfonic acid (2.76 g, 24.46 mmol). Thereaction mixture was stirred at room temperature for 16 h. The reactionwas quenched with ice cold water. The volatiles were evaporated and theresulting material was dried in high vacuum. The residue was dissolvedin saturated NaHCO₃ solution, extracted with chloroform (2×200 mL) andwashed with brine. The organic layer was dried over sodium sulphate andconcentrated to afford crude material. The crude material was purifiedusing a 40 g silica column. The compound was eluted with 50% ethylacetate and pet ether to afford6-bromo-8-iodo-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (2.2 g, 6.51mmol, 53.2% yield) as a light yellow solid. MS (E⁺) m/z: 337.9 (M),R_(t): 1.04 min. [L].

Intermediate F-53

A stirred mixture of6-bromo-8-iodo-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (0.300 g, 0.888mmol), morpholine (0.232 g, 2.66 mmol), and Cs₂CO₃ (0.723 g, 2.219 mmol)in DMF (10.0 mL) was degassed for 5 min. Next, Xantphos (0.051 g, 0.089mmol) and Pd₂(dba)₃ (0.081 g, 0.089 mmol) were added. The reactionmixture was stirred at 120° C. for 2.5 h in a microwave system. Thereaction mixture was diluted with ethyl acetate, filtered and washedwith excess ethyl acetate. The combined organic layers were washed withwater, brine, dried over sodium sulphate, and evaporated to obtain crudematerial. The crude material was purified using a 24 g silica column.The compound was eluted with 80% ethyl acetate and pet ether to afford4-(6-bromo-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)morpholine (0.180g, 0.606 mmol, 68.2% yield) as a light yellow solid. MS (E⁺) m/z: 298.8,R_(t): 1.08 min. [K].

Intermediate F-54:6-bromo-8-cyclopropyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridine

A solution of 6-bromo-8-iodo-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.400 g, 1.184 mmol) and cyclopropylboronic acid (0.305 g, 3.55 mmol)in a mixture of toluene (10.0 mL) and water (2.0 mL) was degassed for 5min. Next, tricyclohexylphosphine (0.066 g, 0.237 mmol), Pd(OAc)₂ (0.027g, 0.118 mmol) and Na₂CO₃ (1.775 mL, 3.55 mmol) were added. The reactionmixture was stirred at 100° C. for 14 h in a sealed tube. The reactionmixture was cooled to room temperature. The mixture was diluted withethyl acetate, filtered, and washed with excess ethyl acetate. Thecombined organic layers were washed with water, brine, dried over sodiumsulphate, and evaporated to afford the crude compound. The crudecompound was purified using a 24 g silica column. The compound waseluted with 35% ethyl acetate and pet ether to afford6-bromo-8-cyclopropyl-2-methyl-[1,2,4]triazolo[1,5-a] pyridine (0.220 g,0.873 mmol, 73.7% yield) as a light yellow solid. MS (E⁺) m/z: 254.0,R_(t): 1.12 min. [K].

Intermediate F-55:6-bromo-8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridine

Intermediate F-55A: 5-bromo-3-iodo-4-methylpyridin-2-amine

To a stirred solution of 5-bromo-4-methylpyridin-2-amine (5.0 g, 26.7mmol), TFA (2.471 mL, 32.1 mmol) in DMF (100 mL) at 0° C. was addedportion-wise NIS (9.02 g, 40.1 mmol). The reaction mixture was stirredat 55° C. for 2 h. The reaction was quenched with ice cold water andsodium thiosulphate solution (3:1). The product was precipitated byadding saturated NaHCO₃ solution (adjust pH-8) and stirring for 10 minat 0° C. The solid compound was collected by filtration to afford5-bromo-3-iodo-4-methylpyridin-2-amine (8 g, 25.6 mmol, 96% yield) as abrown solid. MS (E⁺) m/z: 314.9, R_(t): 0.92 min. [M].

Intermediate F-55B:(E)-N′-(5-bromo-3-iodo-4-methylpyridin-2-yl)-N,N-dimethylformimidamide

A solution of DMF-DMA (10.70 mL, 80 mmol) and5-bromo-3-iodo-4-methylpyridin-2-amine (2.5 g, 7.99 mmol) in DMF (15.0mL) was stirred at 130° C. for 16 h. The reaction mixture was cooled toroom temperature and the volatiles were evaporated. The material wasdried in high vacuum to afford crude(E)-N′-(5-bromo-3-iodo-4-methylpyridin-2-yl)-N,N-dimethylformimidamide(2.8 g, 7.61 mmol, 95% yield) as a brown semi-solid. MS (E⁺) m/z: 370.1,R: 1.59 min. [K].

Intermediate F-55C:6-bromo-8-iodo-7-methyl-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of(E)-N′-(5-bromo-3-iodo-4-methylpyridin-2-yl)-N,N-dimethyl formimidamide(2.8 g, 7.61 mmol) and pyridine (3.08 mL, 38.0 mmol) in methanol (60.0mL) at 0° C. was added hydroxylamine-O-sulfonic acid (1.290 g, 11.41mmol). The reaction mixture was stirred at room temperature for 16 h.The reaction was quenched with ice cold water. The volatiles wereevaporated and the mixture was dried in high vacuum. The residue wasdissolved in saturated NaHCO₃ solution, extracted with chloroform (2×150mL), and washed with brine. The organic layer was dried over sodiumsulphate and concentrated to afford crude product. The crude product waspurified by silica gel chromatography. The compound eluted with 65%ethyl acetate and pet ether to afford6-bromo-8-iodo-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (1.5 g, 4.44mmol, 58.3% yield) as a light yellow solid. MS (E⁺) m/z: 338.2 (M),Retention time: 1.11 min. [K].

Intermediate F-55

A solution of 6-bromo-8-iodo-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.400 g, 1.184 mmol) and cyclopropylboronic acid (0.305 g, 3.55 mmol)in mixture of toluene (15.0 mL) and water (3.0 mL) was degassed for 5min. Next, tricyclohexylphosphine (0.066 g, 0.237 mmol), Pd(OAc)₂ (0.027g, 0.118 mmol) and Na₂CO₃ (1.775 mL, 3.55 mmol) were added. The reactionmixture was stirred at 100° C. for 14 h in a sealed tube.

The reaction mixture was cooled to room temperature, diluted with ethylacetate, filtered, and washed with excess ethyl acetate. The combinedorganic layers were washed with water, brine, dried over sodiumsulphate, and evaporated to afford crude compound. The crude compoundwas purified by silica gel chromatography. The compound eluted with 35%ethyl acetate and pet ether to afford6-bromo-8-cyclopropyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (0.280 g,1.111 mmol, 94% yield) as a light yellow solid. MS (E⁺) m/z: 254.0,R_(t): 2.11 min. [L]

Intermediate F-56:6-bromo-8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine

Intermediate F-56A: 5-bromo-3-methyl-1λ⁴-pyridine-1,2-diamine2,4,6-trimethylbenzenesulfonate

To a stirred solution of ethyl o-mesitylsulfonylacetohydroxamate (3.05g, 10.69 mmol) in dioxane (20 mL) cooled to 0° C. was added perchloricacid (1.074 g, 10.69 mmol). The mixture was stirred at ambienttemperature for 30 min. The reaction mass was quenched with ice coldwater, extracted with dichloromethane (100 mL), dried over sodiumsulphate, and concentrated to afford crude1-amino-5-bromo-3-methyl-1λ⁴-pyridin-2-aminium2,4,6-trimethylbenzenesulfonate. To a stirred solution of5-bromo-3-methylpyridin-2-amine (2 g, 10.69 mmol) in DCM (10 mL) wasadded 1-amino-5-bromo-3-methyl-1λ⁴-pyridin-2-aminium2,4,6-trimethylbenzenesulfonate at 0° C. The reaction mixture wasstirred at ambient temperature for 1 h. The reaction mixture was dilutedwith water (25 mL), extracted with DCM (2×100 mL), dried over sodiumsulphate, and concentrated to afford1,2-diamino-5-bromo-3-methylpyridin-1-ium,2,4,6-trimethylbenzenesulfonateas a white solid (2.1 g, 93%). ¹H NMR (300 MHz, CHLOROFORM-d) δ=7.91(br. s., 1H), 7.63 (d, J=15.9 Hz, 1H), 7.28 (s, 2H), 6.89 (s, 1H), 3.72(s, 1H), 2.81-2.47 (m, 6H), 2.36-2.02 (m, 6H), 1.23 (t, J=7.0 Hz, 2H).

Intermediate F-56

To a stirred solution of1,2-diamino-5-bromo-3-methylpyridin-1-ium,2,4,6-trimethylbenzenesulfonate(1 g, 2.141 mmol) in MeOH (25 mL) at 0° C. was added trifluoroaceticanhydride (0.351 mL, 2.486 mmol). The reaction mixture was stirred for10 min at the same temperature. Next, Et₃N (0.346 mL, 2.486 mmol) wasadded and the reaction mixture was stirred at ambient temperature for 16h. The reaction mixture was concentrated. The reaction was quenched withwater (25 mL). The reaction mixture was extracted with EtOAc (2×100 mL),dried over sodium sulphate, and concentrated to afford6-bromo-8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine. Thecrude mass was purified by silica gel chromatography and eluted in 40%EtOAc in hexane to afford6-bromo-8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (500mg, 71.8%) as off white solid. LC retention time=1.28 min [K]. MS (E⁻)m/z: 280.0 (M+H).

Intermediate F-576-bromo-8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine

Intermediate F-57A: 3,5-dibromo-1λ⁴-pyridine-1,2-diamine2,4,6-trimethylbenzenesulfonate

To a stirred solution of ethyl o-mesitylsulfonylacetohydroxamate (2.266g, 7.94 mmol) in dioxane (20 mL) cooled to 0° C. was added perchloricacid (1.074 g, 10.69 mmol). The reaction mixture was stirred at ambienttemperature for 30 min. The reaction was quenched with ice cold water.The reaction mixture was extracted with dichloromethane (100 mL), driedover sodium sulphate, and concentrated to afford crude1-amino-3,5-dibromo-1λ⁴-pyridin-2-aminium2,4,6-trimethylbenzenesulfonate. To a stirred solution of3,5-dibromopyridin-2-amine (2 g, 7.94 mmol) in DCM (10 mL) was added1-amino-3,5-dibromo-1λ⁴-pyridin-2-aminium2,4,6-trimethylbenzenesulfonate at 0° C. The reaction mixture wasstirred at ambient temperature for 1 h. The reaction mixture was dilutedwith water (25 mL), extracted with DCM (2×100 mL), dried over sodiumsulphate, and concentrated to afford1,2-diamino-3,5-dibromopyridin-1-ium, 2,4,6-trimethylbenzenesulfonate asa white solid (2.1 g, 93.5%). ¹H NMR (400 MHz, DMSO-d₆) δ=7.88 (d, J=2.0Hz, 1H), 7.70 (d, J=2.0 Hz, 1H), 7.12 (s, 1H), 6.70 (s, 4H), 3.56 (s,1H), 2.10 (s, 6H).

Intermediate F-57B:6,8-dibromo-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of 1,2-diamino-3,5-dibromopyridin-1-ium,2,4,6-trimethylbenzenesulfonate (1 g, 2.141 mmol) in MeOH (25 mL) cooledto 0° C. was added trifluoroacetic anhydride (0.351 mL, 2.486 mmol). Thereaction mixture was stirred for 10 mins. After Et₃N (0.346 mL, 2.486mmol) was added, the reaction mixture was stirred at ambient temperaturefor 16 h. The reaction mixture was concentrated, quenched with water (25mL), extracted with EtOAc (2×100 mL), dried over sodium sulphate, andconcentrated to afford6,8-dibromo-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine. Thecrude mass was purified by silica gel chromatography, and eluted with40% EtOAc in hexane to afford6,8-dibromo-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (650 mg,73.8%) as off white solid. LC retention time=1.37 min [K]. MS (E⁻) m/z:344.0 (M+H).

Intermediate F-57

To a solution of6,8-dibromo-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine (350 mg,1.015 mmol) in acetonitrile (15 mL) was added sodium methoxide (54.8 mg,1.015 mmol). The resulting mixture was stirred at 85° C. for 1 h. Thereaction mixture was quenched with water (20 mL), extracted with EtOAc(2×50 mL), dried over sodium sulphate, and concentrated to afford6-bromo-8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine.The crude mass was purified by silica gel chromatography, and was elutedwith 50% EtOAc in hexane to afford6-bromo-8-methoxy-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine(160 mg, 53.5%) as white solid. LC retention time=1.26 min [K]. MS (E⁻)m/z: 294.0 (M−H).

Intermediate F-58: 6-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Commercially available reagent: CAS No 356560-80-0.

Intermediate F-59:6-chloro-8-trideuteromethyl-[1,2,4]triazolo[1,5-a]pyridine

8-bromo-6-chloro-[1,2,4]triazolo[1,5-a]pyridine was prepared followingthe general procedure for F-2 starting from3-bromo-5-chloropyridin-2-amine. LC retention time 0.67 min [TS1]. MS(ES⁺) m/z: 233.9 (M+H).

A solution of 8-bromo-6-chloro-[1,2,4]triazolo[1,5-a]pyridine (150 mg,0.645 mmol) in THF (5.0 mL) was degassed with nitrogen gas for 5minutes. Iron (III) acetylacetonate (22.79 mg, 0.065 mmol) was added.The light yellow solution became red and was degassed again, and thenevacuated and backfilled with nitrogen gas three times.Trideuteromethylmagnesium iodide (0.97 mL, 0.97 mmol) was added and thereaction mixture was stirred for 30 minutes at room temperature. Uponcompletion, the reaction mixture was diluted with dichloromethane (20mL), ammonium chloride (10 mL) and water (10 mL). The layers wereseparated, and the aqueous layer was extracted with dichloromethane(2×15 mL). The combined organic layers were dried over sodium sulfate,filtered, and concentrated to afford a crude residue, which was purifiedusing silica gel chromatography eluting with hexanes/ethyl acetate 0-70%to afford 6-chloro-8-trideuteromethyl-[1,2,4]triazolo[1,5-a]pyridine (41mg, 0.240 mmol, 37.2% yield). LC retention time 0.64 min [TS1]. MS (ES⁺)m/z: 171.08 (M+H). ¹H NMR (400 MHz, CHLOROFORM-d) δ 8.50 (d, J=2.0 Hz,1H), 8.30 (s, 1H), 7.29 (d, J=2.0 Hz, 1H).

Example 16-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 1A: tert-butyl4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

To a stirred solution of tert-butyl4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(50 mg, 0.107 mmol), 6-bromo-[1,2,4]triazolo[1,5-a]pyridine (31.7 mg,0.160 mmol) in tetrahydrofuran (5 mL), and water (0.5 mL) was addedpotassium phosphate tribasic (68.0 mg, 0.320 mmol). The solution wasdegassed with nitrogen for 10 mins. Next, PdCl₂(dppf) (7.81 mg, 10.67μmol) was added and the solution was degassed again for 10 mins. Thereaction mixture was heated to 75° C. for 16 h. The reaction progresswas monitored by LCMS. The reaction mass was filtered through a celitebed, washed with EtOAc, and concentrated to afford tert-butyl4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (50 mg, 0.109 mmol). The material was carriedon directly into the subsequent step without further purification.

Example 1

To a stirred solution of tert-butyl4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (50 mg, 0.109 mmol) in DCM (2 mL) was added 1,4-dioxane (4N HCl)(0.2 mL). The reaction mixture was stirred at room temperature for 16 h.The progress of the reaction was monitored by LCMS. The reaction mixturewas concentrated and the crude material was purified by preparativeLC/MS with the following conditions: Waters Xbridge C18, 19×150 mm, 5μm; Guard Column: Waters XBridge C18, 19×10 mm, 5 μm; Mobile PhaseA:5:95 acetonitrile:water with 0.1% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.1% TFA; Gradient: 2-20% B over 25 minutes,followed by a 10 minute hold at 20% B and 5 minute hold at 100% B; Flow:15 mL/min. Fractions containing the product were combined and driedusing a Genevac centrifugal evaporator. The yield of the product was 5.4mg, and its estimated purity by LCMS analysis was 100%. Two analyticalLC/MS injections were used to determine the final purity. Injection 1conditions: Column: Ascentis Express C18(50×2.1) mm, 2.7 μm; MobilePhase A: 5:95 Acetonitrile:water with 10 mM NH₄OAc; Mobile Phase B: 95:5Acetonitrile:water with 10 mM NH₄OAc; Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow: 1.1 mL/min. Injection 2 conditions:Column: Ascentis Express C18(50×2.1) mm, 2.7 μm; Mobile Phase A: 5:95acetonitrile:water with 0.1% TFA; Mobile Phase B: 95: 5Acetonitrile:water with 0.1% TFA; Temperature: 50° C.; Gradient: 0-100%B over 3 minutes; Flow: 1.1 mL/min. LCMS MH⁺=360 Ret. Time=0.66 min[A1]; Proton NMR was acquired in deuterated DMSO. ¹H NMR (400 MHz,DMSO-d₆) δ=11.24 (s, 1H), 9.01 (d, J=1.0 Hz, 1H), 8.66-8.55 (m, 1H),8.03-7.96 (m, 1H), 7.79 (dd, J=9.0, 1.5 Hz, 1H), 7.57 (s, 1H), 7.35 (d,J=8.5 Hz, 1H), 7.02 (dd, J=8.3, 1.3 Hz, 1H), 3.41 (d, J=12.0 Hz, 2H),3.30-3.23 (m, 1H), 3.10-3.00 (m, 2H), 2.96-2.90 (m, 1H), 2.03-1.94 (m,2H), 1.91-1.84 (m, 2H), 1.45 (d, J=7.0 Hz, 6H).

Example 26-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridinehydrochloride

Intermediate 2A: tert-butyl4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

The preparation was performed in two batches and combined for workup.

Batch #1: To a mixture of tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (10 g,23.73 mmol), bis(benzonitrile)palladium(II) chloride (0.182 g, 0.475mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.390 g, 0.949mmol) in dioxane (80 mL) under nitrogen were added pinacolborane (8.61mL, 59.3 mmol) and triethylamine (6.62 mL, 47.5 mmol). The mixture washeated at 85° C. for 5 min. After cooling down to room temperature, 2 Mpotassium phosphate tribasic solution (35.6 mL, 71.2 mmol) was addedslowly. Next, 6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (4.53 g,21.36 mmol) was added, followed by PdCl₂(dppf)-CH₂Cl₂ adduct (0.775 g,0.949 mmol). The reaction mixture was stirred for 30 min at 65° C.

Batch #2: In a 1 L round bottom flask, pinacolborane (25.8 mL, 178 mmol)and triethylamine (19.85 mL, 142 mmol) were added to a mixture oftert-butyl 4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(30 g, 71.2 mmol), bis(benzonitrile) palladium(II) chloride (0.546 g,1.424 mmol), and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.169g, 2.85 mmol) in dioxane (240 mL) under nitrogen. The mixture was heatedat 85° C. for 5 min. After cooling down to room temperature, 2 Mpotassium phosphate tribasic solution (107 mL, 214 mmol) was added veryslowly first for the first 10 mL. When there were no more bubbles, theremainder of the K₃PO₄ solution was rapidly added, followed by theadditions of 6-bromo-8-methyl-[1,2,4]triazolo[1,5-a] pyridine (13.59 g,64.1 mmol) and PdCl₂(dppf)-CH₂Cl₂ adduct (2.326 g, 2.85 mmol). Thereaction mixture was stirred for 1 h at 65° C.

The two batches were combined for workup. The aqueous layer was removedand the organic layer was washed with brine, dried over Na₂SO₄, filteredthrough a Celite pad, and concentrated to give a dark oil (87 g). Thematerial was purified by silica gel chromatography (hexanes/ethylacetate as eluent) affording 29 grams of the product. LCMS MH⁺=430.1Ret. Time=0.63 min [C1]; ¹H NMR (400 MHz, DMSO-d₆) δ 11.11 (s, 1H), 8.80(d, J=0.7 Hz, 1H), 8.53 (s, 1H), 7.65-7.52 (m, 2H), 7.30 (d, J=8.4 Hz,1H), 7.02 (dd, J=8.4, 1.5 Hz, 1H), 4.19-4.04 (m, 2H), 3.28-3.19 (m, 1H),2.96-2.70 (m, 3H), 2.63 (s, 6H), 2.38-2.26 (m, 1H), 1.80 (d, J=12.6 Hz,2H), 1.56 (qd, J=12.4, 4.0 Hz, 2H), 1.47-1.38 (m, 12H).

Alternative Preparation of Intermediate 2A

To a 500 mL round bottle flask were added tert-butyl4-(2-bromo-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (11 g,26.1 mmol), bis(benzonitrile)palladium(II) chloride (0.200 g, 0.522mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.429 g, 1.044mmol) and dioxane (87 mL). Nitrogen was bubbled through the reactionmixture for 5 min. Next, pinacolborane (9.47 ml, 65.3 mmol) andtriethylamine (9.10 ml, 65.3 mmol) were added to the reaction mixture.The triethylamine was added in small potions slowly for the first ⅓ andthen the rest ⅔ was added quickly. The reaction mixture was heated at85° C. for 10 min under N₂. The reaction temperature reached 100° C. Thereaction mixture was cooled to room temperature with an ice-water bath.Next, 2 M potassium phosphate tribasic solution (39.2 mL, 78 mmol) wasadded. The first 1/10 was added slowly. When there was no more bubbles,the remainder of the K₃PO₄ solution was added, followed by6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (4.98 g, 23.49 mmol),PdCl₂(dppf)-CH₂Cl₂ adduct (0.853 g, 1.044 mmol) washed in with dioxane(10 mL). The mixture was heated at 65° C. for 1 h under N₂. After themixture was cooled to room temperature, the organic layer and theaqueous layer was separated. EtOAc was used to wash the flask during thetransfer. The organic layer was washed with brine, dried over Na₂SO₄,filtered through a Celite pad and concentrated to give 44.4 g crude oil.It was purified with silica gel chromatography using a 1.5 kg silicacolumn. The column was eluted with hexane and ethyl acetate. The productwas eluted at 60% ethyl acetate:hexane to afford tert-butyl4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(9.27 g, 19.58 mmol, 75% yield) as a lighted tinted foam. LCMS MH⁺:474.3; HPLC Ret. Time 1.15 min. Method G. ¹H NMR (400 MHz, CHLOROFORM-d)δ 8.61-8.54 (m, 1H), 8.43-8.38 (m, 1H), 7.96-7.88 (m, 1H), 7.70-7.64 (m,1H), 7.48-7.44 (m, 1H), 7.40-7.35 (m, 1H), 7.17-7.09 (m, 1H), 4.40-4.23(m, 2H), 3.40-3.26 (m, 1H), 2.75 (s, 6H), 1.98-1.89 (m, 2H), 1.85-1.67(m, 2H), 1.53 (m, 12H), 1.52-1.49 (s, 3H).

Example 2

To a stirred solution of tert-butyl4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(29 g, 61.2 mmol) in DCM (102 mL), was added 4 M HCl in dioxane (77 mL,306 mmol) through a syringe. The temperature was observed to increasedseveral degrees. The solution turned into a suspension during theaddition, then a clear solution, then a heavy suspension again. MeOH(306 mL) was added to give a clear solution. LCMS showed the reactionwas close to completion after 2.5 hr at room temperature. The reactionmixture was concentrated under reduced pressure with a water bath (T=45°C.) and then diluted with diethyl ether (200 mL). The product wascollected by filtration to afford6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridinedihydrochloride. LC-MS: M+1=374, rt=0.80 min., [A1]; ¹H NMR (400 MHz,DMSO-d₆) δ 11.10 (s, 1H), 8.80 (d, J=0.7 Hz, 1H), 8.54 (s, 1H),7.66-7.50 (m, 2H), 7.30 (d, J=8.3 Hz, 1H), 7.02 (dd, J=8.4, 1.5 Hz, 1H),4.09 (q, J=5.3 Hz, 1H), 3.38-3.23 (m, 6H), 3.18 (d, J=5.3 Hz, 2H), 3.06(d, J=11.5 Hz, 1H), 2.74-2.59 (m, 4H), 1.75 (d, J=10.0 Hz, 2H),1.68-1.52 (m, 2H), 1.51-1.37 (m, 6H).

Alternative Preparation of Example 2

To a stirred solution of tert-butyl4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(7.45 g, 15.73 mmol) in DCM (40 mL) was added 4 M HCl in dioxane (35.4mL, 142 mmol) through a syringe at room temperature. The solution turnedto a suspension during the addition, then a clear solution, then a heavysuspension again. MeOH (100 mL) was added to give a clear solution. Thereaction was complete in 2 h. The reaction mixture was concentratedunder reduced pressure and then diluted with diethyl ether (200 mL). Thedesired product HCl salt was collected by filtration to afford6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine hydrochloride (6.4 g, 15.64 mmol, 99.4% yield) as a yellow.LCMS MH⁺: 374.1; HPLC Ret. Time 0.64 min. Method G.

The following examples were prepared according to the general proceduresdisclosed in Examples 1 and 2.

TABLE 3 Ex. LCMS Rt No. Structure Interm. [M + H] (min) Method 3

F-3 374.3 1.07 QC- ACN- TFA- XB 4

F-4 388.3 1.26 QC- ACN- AA- XB 5

F-5 390.3 1.02 Method E 6

F-6 404.3 1.21 QC- ACN- AA- XB

Example 46-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrid

To a stirred suspension of tert-butyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(37.8 g, 78 mmol) in DCM (97 ml) and MeOH (291 ml) was added 4 M HCl indioxane (97 mL, 388 mmol) at room temperature to give a clear solution.After a few hours, the reaction mixture became a white suspension. Thereaction was complete after 4 h. The reaction mixture was concentratedunder reduced pressure and then diluted with diethyl ether (250 mL). Theproduct bis-HCl salt was collected by filtration to afford6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine,2 HCl (34.66 g, 75 mmol, 97% yield) as an off-white solid. LCMS MH⁺:388.3; HPLC Ret. Time 1.26 min. Method QC-ACN-AA-XB. ¹H NMR (500 MHz,DMSO-d₆) δ 11.08-10.95 (m, 1H), 8.77-8.67 (m, 1H), 8.55-8.41 (m, 1H),7.64-7.48 (m, 1H), 7.39-7.27 (m, 1H), 7.05-6.94 (m, 1H), 3.47-3.34 (m,1H), 3.11-2.99 (m, 2H), 2.98-2.82 (m, 2H), 2.61-2.57 (m, 3H), 2.56-2.54(m, 1H), 2.18-2.13 (m, 3H), 2.03-1.83 (m, 4H), 1.39-1.26 (m, 6H).

Example 56-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridinedihydrochloride

To a stirred suspension of tert-butyl4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(46.5 g, 95 mmol) in DCM (47.5 mL) and MeOH (190 mL), was added 4M HClin dioxane (119 mL, 475 mmol) at room temperature. After 1 h, the clearsolution became a white suspension. MeOH (50 mL) was added and thesuspension was stirred for another hour. The reaction mixture wasconcentrated under reduced pressure and then diluted with diethyl ether(300 mL). The desired product HCl salt was collected by filtration anddried for two days to afford6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridinedihydrochloride (33.6 g, 72.7 mmol, 76% yield) as an off-white solid.LCMS MH₊: 390.1. HPLC Ret. Time 0.64 min. Method G.

Example 72-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide

Triethylamine (9.70 mL, 69.6 mmol) and 2-chloro-N-methylacetamide (2.246g, 20.88 mmol) were added to a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (2.6 g, 6.96 mmol) in THF (50 mL). The reactionmixture was stirred at room temperature for 12 h. The reaction mass wasconcentrated under vacuum and the residue obtained was quenched with 150mL ice cold water resulting in the formation of a precipitate. Thesolids were collected by vacuum filtration and air dried. The collectedsolids were further dried under vacuum for 15 h to afford2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N-methylacetamide (1.5 g) as an off-white solid. ¹H NMR(400 MHz, DMSO-d₆) δ 1.42 (d, J=7.20 Hz, 6H), 1.69-1.72 (m, 4H),1.75-1.81 (m, 1H), 2.78-2.82 (m, 6H), 2.85-2.88 (m, 4H), 3.25-3.31 (m,2H), 7.05 (dd, J=1.60, 8.40 Hz, 1H), 7.31 (d, J=8.40 Hz, 1H), 7.59 (d,J=10.00 Hz, 2H), 7.72-7.73 (m, 1H), 8.54 (s, 1H), 8.81 (s, 1H), 11.12(s, 1H). LCMS for molecular formula C₂₆H₃₂N₆O was 444.264; found 445(M⁺). Waters Xbridge C18, 19×150 mm, 5 μm; Guard Column: Waters XBridgeC18, 19×10 mm, 5 μm; Mobile Phase A:5:95 Acetonitrile:water with 10 mMNH₄OAc; Mobile Phase B: 95:5 Acetonitrile:water with 10 mM NH₄OAc;Gradient: 10-50% B over 25 minutes, followed by a 10 minute hold at 50%B and 5 minute hold at 100% B; Flow: 15 mL/min. RT Min: 1.91, Wavelength: 220 nm. HPLC: XBridge Phenyl (4.6×150) mm, 3.5 μm SC/749 Buffer:0.05% TFA in water pH 2.5 Mobile Phase A: Buffer:ACN (95:5) Mobile PhaseB: ACN:Buffer (95:5) FLOW: 1 mL/min TIME B % 0 10, 12 100, 15 100.Retention Time: 6.19 minutes.

The following examples were prepared according to the general proceduresdisclosed in Example 7.

TABLE 4 Ex. LCMS R_(t) No. Structure MH⁺ (min) Method  8

413.3 1.28 QC- ACN- TFA- XB  9

427.2 1.82 QC- ACN- AA- XB 10

430 1.57 QC- ACN- AA- XB 11

431.4 1.24 QC- ACN- AA- XB 12

446.3 1.707 Method E 13

427.3 1.46 QC- ACN- TFA- XB 14

441.3 1.27 QC- ACN- TFA- XB 15

445 1.19 QC- ACN- TFA- XB 16

459.5 1.71 QC- ACN- AA- XB 17

460 1.7 QC- ACN- AA- XB 18

494.3 1.71 QC- ACN- AA- XB 19

495.2 1.62 QC- ACN- AA- XB 20

520.5 1.31 QC- ACN- TFA- XB 21

429.2 1.94 Method E 22

447.2 1.64 Method E 23

461.2 1.73 Method E 24

462.4 1.40 Method E 25

475.4 1.37 Method E

Example 132-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile

To a 1 dram vial were added6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridinehydrochloride (0.050 g, 0.118 mmol), NMP, and DBU (0.025 ml, 0.164mmol). The material went into solution and 2-bromoacetonitrile (0.014 g,0.118 mmol) was added. The reaction vial was capped. The reactionmixture was stirred overnight at room temperature. The sample wasdiluted with solvent (90:10:0.1 CH₃CN:water:TFA), filtered, and purifiedwith preparative HLPC. The crude material was purified via preparativeLC/MS with the following conditions: Column: XBridge C18, 19×200 mm, 5μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mMammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mMammonium acetate; Gradient: 30-70% B over 20 minutes, then a 5-minutehold at 100% B; Flow: 20 mL/min. Fractions containing the desiredproduct were combined and dried via centrifugal evaporation to afford2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetonitrile (16.8 mg, 0.039 mmol, 32.7% yield). LCMSMH⁺: 427.1. HPLC Ret. Time 1.30 min. Method QC-ACN-TFA-XB. ¹H NMR (500MHz, DMSO-d₆) δ 8.77-8.69 (m, 1H), 8.50-8.35 (m, 1H), 7.61-7.51 (m, 1H),7.33-7.23 (m, 1H), 7.08-6.93 (m, 1H), 3.44-3.34 (m, 1H), 2.98-2.83 (m,3H), 2.63-2.56 (m, 4H), 2.56-2.53 (m, 2H), 2.39-2.28 (m, 2H), 2.21-2.12(m, 3H), 1.90-1.69 (m, 4H), 1.37-1.26 (m, 6H).

Example 152-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide

To a reaction flask were added6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine,2 HCl (47.66 g, 104 mmol), DCE (220 mL), DBU (62.4 mL, 414 mmol), and2-bromoacetamide (17.14 g, 124 mmol). The reaction flask was capped. Thereaction mixture was stirred overnight at room temperature. The reactionmixture was concentrated, diluted with water, and stirred for 30 minutesthen filtered. The solid was recrystallized using ethanol to afford2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide(42.3 g, 93 mmol, 90% yield) as a white solid. LCMS MH⁺: 445. HPLC Ret.Time 1.20 min. Method QC-ACN-TFA-XB. ¹H NMR (400 MHz, DMSO-d₆) δ10.97-10.86 (m, 1H), 8.78-8.69 (m, 1H), 8.54-8.40 (m, 1H), 7.64-7.49 (m,1H), 7.30-7.21 (m, 2H), 7.17-7.09 (m, 1H), 7.06-6.93 (m, 1H), 2.99-2.82(m, 5H), 2.62-2.54 (m, 4H), 2.24-2.12 (m, 5H), 1.92-1.72 (m, 4H),1.37-1.29 (m, 6H).

Example 186-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine

Preparation 1:

To a 40 ml vial was added6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(0.800 g, 2.064 mmol), DCM (5 mL) and DBU (0.622 mL, 4.13 mmol). Thematerial went into solution and 2-bromoacetamide (0.299 g, 2.168 mmol)was added. The reaction vial was capped. The reaction mixture wasstirred overnight at room temperature. The reaction mixture was dilutedwith water and extracted with DCM. The organics were washed with brine,dried over Na₂SO₄, filtered and concentrated. The residue was dissolvedin minimal DCM and purified by silica gel chromatography, eluting with0-10% MeOH/DCM. Following concentration of the fractions, the productwas collected as a white solid (0.6 g). To this was added 40 mL of a 10%MeOH/ethyl acetate solution and the suspension was taken to a boil. Thesolids were filtered off and rinsed with hot MeOH/ethyl acetate (1:10).The filtrate was reheated and capped to recrystallize. After 3 days, thewhite solid was filtered off and washed with ethyl acetate, then ether,and dried on the vacuum pump overnight to afford2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)acetamide(480 mg, 1.07 mmol, 51.8% yield). MS (M^(t1)) m/z: 445.3 (MH⁺). LCretention time 0.69 min [G]. ¹H NMR (400 MHz, DMSO-d₆) δ 11.00-10.85 (m,1H), 8.79-8.69 (m, 1H), 8.53-8.43 (m, 1H), 7.60-7.49 (m, 1H), 7.32-7.21(m, 2H), 7.18-7.11 (m, 1H), 7.06-6.99 (m, 1H), 3.00-2.83 (m, 5H),2.63-2.55 (m, 4H), 2.24-2.12 (m, 5H), 1.92-1.72 (m, 4H), 1.40-1.24 (m,6H).

Preparation 2:

To a reaction vial were added6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine,2 HCl (40 g, 87 mmol), DCE (280 mL), and DBU (45.8 mL, 304 mmol). Thematerial went into solution and 1-bromo-2-(methylsulfonyl) ethane (18.46g, 99 mmol) was added. The reaction mixture was stirred overnight atroom temperature under N₂. The sample was concentrated, diluted withwater, stirred for 30 minutes, and then filtered. The solid wasrecrystallized using EtOH to afford6-(3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl[1,2,4]triazolo[1,5-a]pyridine (40 g, 81 mmol, 93% yield) as a white solid. LCMS MH⁺:494.3; HPLC Ret. Time 1.70 min. Method QC-ACN-AA-XB. ¹H NMR (400 MHz,CHLOROFORM-d) δ 8.45-8.38 (m, 1H), 8.37-8.30 (m, 1H), 8.18-8.12 (m, 1H),7.69-7.62 (m, 1H), 7.43-7.35 (m, 1H), 7.19-7.12 (m, 1H), 3.29-3.20 (m,2H), 3.16-3.07 (m, 5H), 3.02-2.92 (m, 3H), 2.74-2.67 (m, 1H), 2.66-2.60(m, 3H), 2.31-2.22 (m, 2H), 2.21-2.17 (m, 3H), 2.07-1.79 (m, 4H),1.42-1.35 (m, 6H).

Example 252-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide

Preparation 1:

To a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(0.05 g, 0.128 mmol) in THF (2 mL) and DMF (1 mL) solvent mixture wereadded 2-chloro-N,N-dimethylacetamide (0.023 g, 0.193 mmol) and TEA(0.179 mL, 1.284 mmol) at room temperature. The reaction mixture wasstirred at room temperature for 24 h. The reaction mixture wasconcentrated under vacuum. To the solid material was added water (5 mL)and extracted with ethyl acetate. The organic layer was dried overNa₂SO₄, filtered and concentrated under vacuum. The crude material waspurified via preparative LC/MS with the following conditions: Column:Waters XBridge C18, 19×150 mm, 5 μm particles; Mobile Phase A: 10 mMammonium acetate; Mobile Phase B: methanol; Gradient: 10-50% B over 30minutes, then a 5-minute hold at 100% B; Flow: 15 mL/min. Fractionscontaining the product were combined and dried via centrifugalevaporation to afford2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(14.2 mg, 0.03 mmol, 23.31% yield). MS (M⁺¹) m/z: 475.4 (MH⁺). LCretention time 1.38 min [A]. ¹H NMR (400 MHz, DMSO-d₆) δ 11.38 (s, 1H),8.83-8.75 (m, 2H), 7.83 (s, 1H), 7.57 (d, J=8.3 Hz, 1H), 7.41 (d, J=1.2Hz, 1H), 7.30 (dd, J=8.4, 1.6 Hz, 1H), 4.34 (s, 3H), 3.43 (d, J=5.9 Hz,3H), 3.34 (s, 4H), 3.22 (d, J=11.0 Hz, 4H), 3.09 (s, 3H), 2.79 (d, J=1.7Hz, 3H), 2.48-2.38 (m, 2H), 2.15 (s, 5H), 2.08-1.95 (m, 4H), 1.72 (d,J=7.1 Hz, 6H).

Preparation 2:

To a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine,HCl (30.6 g, 71.8 mmol) in a DMF (700 mL) solvent mixture were added2-chloro-N,N-dimethylacetamide (9.62 mL, 93 mmol) and TEA (50.1 mL, 359mmol) at room temperature. The reaction mixture was stirred at roomtemperature for 12 h. The starting material was converted to product.Next, water (2 L) was added to the above solution, the upper layer andthe lower layer were extracted with ethyl acetate. The combination ofthe organic layers was washed with brine, dried and concentrated to givea solid, which was purified by recrystallization from ethanol to afford2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(28.3 g, 59.3 mmol, 83% yield). LCMS MH⁺: 475.2. HPLC Ret. Time 0.66min. Method G. C: 68.28%, H: 7.19%, N: 17.63%.

Example 266-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine

To a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridinehydrochloride (24.5 g, 59.8 mmol) in DCM (610 mL) were addedtriethylamine (24.19 g, 239 mmol), oxetan-3-one (17.23 g, 239 mmol),acetic acid (7.18 g, 120 mmol), and sodium triacetoxyborohydride (50.7g, 239 mmol). The solution was stirred at room temperature. After 5 min,LCMS showed 20% conversion; and after overnight, HPLC showed no startingmaterial. The solvent was removed under vacuum. The residue wasdissolved in 500 mL ethyl acetate and washed with saturated NaHCO₃solution (4×300 mL), dried over Na₂SO₄, and concentrated under reducedpressure. The residue was purified by recrystallization from a mixtureof EtOH/water (20/80), dried to afford6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a] pyridine (24.6 g, 57.0 mmol, 95% yield) as a white solid. LCMSMH⁺=430.1 Ret. Time=0.63 min; Column: BEH C18 2.1×50 mm 1.7 μm Vial:3:1; HPLC Ret. Time 7.86 min. Waters XSelect CSH C18 2.5 μM 4.6 μM×7.5mm. Solvent A: H₂O w/0.1% TFA. Solvent B ACN w/0.1% TFA. GradientComplex Start % B 10% 16 min 45% B 20 min 90% 24 min 90% 25 min 10% Stoptime 25 min Flow Rate 1.5 mL/min. ¹H NMR (500 MHz, DMSO-d₆) δ 11.11 (s,1H), 8.75 (s, 1H), 8.51 (s, 1H), 7.56 (d, J=16.5 Hz, 2H), 7.30 (d, J=8.4Hz, 1H), 7.03 (d, J=8.3 Hz, 1H), 4.64-4.33 (m, 4H), 4.72-4.27 (m, 4H),3.65 (br. s., 2H), 3.47-3.12 (m, 2H), 2.79 (d, J=10.4 Hz, 2H), 2.61 (s,3H), 1.99-1.59 (m, 7H), 1.41 (d, J=6.8 Hz, 6H).

Alternative Preparation of Example 26

To a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridinehydrochloride (24.5 g, 59.8 mmol) in DCM (610 ml) were addedtriethylamine (24.19 g, 239 mmol), oxetan-3-one (17.23 g, 239 mmol),acetic acid (7.18 g, 120 mmol) and sodium triacetoxyborohydride (50.7 g,239 mmol). The solution was stirred at room temperature, after 5 min thereaction progressed 20%. The reaction went to completion overnight. Thesolvent was removed under reduced pressure. The residue was dissolved in500 mL ethyl acetate and washed with saturated NaHCO₃ solution (300mL×4), dried over Na₂SO₄, and concentrated under reduced pressure toafford the crude product. The crude material was purified to remove Pdin the treatment described below and recrystallized from a mixture ofEtOH/water (20/80) and dried to afford 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(24.6 g, 57.0 mmol, 95% yield) as a solid. LCMS MH⁺: 430.1; HPLC Ret.Time 0.63 min. Method G; ¹H NMR (400 MHz, DMSO-d₆) δ 11.18-11.05 (m,1H), 8.88-8.76 (m, 1H), 8.58-8.47 (m, 1H), 7.64-7.54 (m, 2H), 7.34-7.26(m, 1H), 7.09-6.96 (m, 1H), 4.61-4.53 (m, 2H), 4.51-4.42 (m, 2H),3.48-3.37 (m, 1H), 3.31-3.20 (m, 1H), 2.86-2.78 (m, 2H), 2.68-2.63 (m,3H), 2.63-2.55 (m, 1H), 1.96-1.68 (m, 6H), 1.49-1.38 (m, 6H).

Pd Removal Procedure: The sample was treated to remove Pd using thefollowing steps: 1. The crude sample was dissolved in 500 mL THF andtreated with SiliaMetS@DMT (40 g, from SiliCycle). The solution wasstirred overnight at room temperature under N₂. 2. After filtration, thesolvent was removed and the residue was dissolved in AcOEt and washedwith brine and dried. 3. After concentration, the residue wasrecrystallized from EtOH-water (20/80) to afford the product.

The following examples were prepared according to the general procedureof Examples 26.

TABLE 5 Ex. LCMS R_(t) No. Structure MH⁺ (min) Method 27

416.4 2.39 Method F 28

416 1.43 QC-ACN-AA-XB 29

430.1 1.7 QC-ACN-AA-XB 30

454.2 1.29 QC-ACN-TFA-XB 31

455.3 1.54 QC-ACN-AA-XB 32

455.2 1.22 QC-ACN-TFA-XB 33

455.4 1.11 QC-ACN-TFA-XB 34

455.9 1.13 QC-ACN-AA-XB 35

458.4 1.33 QC-ACN-AA-XB 36

459.3 1.37 Method A 37

506.3 1.43 QC-ACN-AA-XB 38

444.3 1.24 QC-ACN-TFA-XB 39

469.2 1.46 QC-ACN-AA-XB 40

471.9 1.47 QC-ACN-AA-XB 41

473.4 1.41 QC-ACN-AA-XB 42

483 1.52 QC-ACN-AA-XB 43

483 1.68 QC-ACN-AA-XB 44

446.2 1.91 Method E 45

474.4 1.31 Method E

6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine

To a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridinedihydrochloride (39.7 g, 86 mmol) in DCM (859 ml) was addedtriethylamine (34.8 g, 343 mmol), oxetan-3-one (24.75 g, 343 mmol),acetic acid (10.31 g, 172 mmol) and sodium triacetoxyborohydride (72.8g, 343 mmol). The solution was stirred at room temperature. After 9 h,the starting material was no longer detected. The solvent was removed byrotavapor. The residue was dissolved in 1500 mL ethyl acetate and washedwith saturated NaHCO₃ solution (500 mL×4), dried over Na₂SO₄, andconcentrated under reduced pressure to give residue. The residue waspurified by recrystallization from a mixture of EtOH/water (60/40) twotimes, dried to give 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-indol-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine(32.3 g, 72.2 mmol, 84% yield) as a white solid. LCMS MH⁺: 446.1. HPLCRet. Time 0.63 min. Method G. ¹H NMR (400 MHz, CHLOROFORM-d) δ 8.42-8.31(m, 2H), 8.20-8.10 (m, 1H), 7.77-7.67 (m, 1H), 7.44-7.36 (m, 1H),7.31-7.26 (m, 1H), 7.21-7.12 (m, 1H), 6.95-6.85 (m, 1H), 4.80-4.63 (m,4H), 4.12-4.03 (m, 3H), 3.62-3.51 (m, 1H), 3.42-3.25 (m, 1H), 3.02-2.87(m, 2H), 2.73-2.58 (m, 1H), 2.10-1.85 (m, 6H), 1.55-1.44 (m, 6H).

Example 462-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one

To a solution of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (75 mg, 0.201 mmol) in DMF (1 mL) were added TEA(0.140 mL, 1.004 mmol), 2-(dimethylamino)acetic acid (20.71 mg, 0.201mmol), and HATU (76 mg, 0.201 mmol). The reaction mixture was stirred atroom temperature for 12 h. The reaction mass was diluted with methanol(2 mL) and passed through a syringe pad to filter away inorganics, andthen purified by reverse phase preparative chromatography. The crudematerial was purified via preparative LC/MS with the followingconditions: Column: Waters XBridge C18, 19×150 mm, 5-μm particles;Mobile Phase A: 10-mM ammonium acetate; Mobile Phase B: acetonitrile;Gradient: 20-60% B over 30 minutes, then a 5-minute hold at 100% B;Flow: 15 mL/min. Fractions containing the product were combined anddried via centrifugal evaporation. The yield of the product was 11.7 mg,and its estimated purity by LCMS analysis was 96%. Two analytical LC/MSinjections were used to determine the final purity. Injection 1conditions: Column: Ascentis Express C18(50×2.1) mm, 2.7 μm; MobilePhase A: 5:95 Acetonitrile:water with 10 mM NH₄OAc; Mobile Phase B: 95:5Acetonitrile:water with 10 mM NH₄OAc; Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow: 1.1 mL/min. Injection 2 conditions:Column: Ascentis Express C18 (50×2.1) mm, 2.7 μm; Mobile Phase A: 5:95Acetonitrile:water with 0.1% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.1% TFA; Temperature: 50° C.; Gradient: 0-100%B over 3 minutes; Flow: 1.1 mL/min. ¹H-NMR (400 MHz, DMSO-d₆): δ 1.12(d, J=6.00 Hz, 3H), 1.44 (d, J=6.80 Hz, 6H), 1.69-1.72 (m, 2H),1.75-1.81 (m, 2H), 2.32-2.34 (m, 1H), 2.50 (s, 3H), 2.62-2.71 (m, 4H),2.80-2.94 (m, 1H), 3.25-3.32 (m, 2H), 3.54-3.58 (m, 2H), 4.00-4.07 (m,1H), 4.60 (d, J=11.20 Hz, 1H), 7.04 (dd, J=1.20, 8.40 Hz, 1H), 7.30 (d,J=8.40 Hz, 1H), 7.58 (d, J=8.80 Hz, 1H), 8.53 (s, 1H), 8.80 (s, 1H),11.11 (s, 1H). LCMS for molecular formula C₂₆H₃₂N₆O was 444.264, found445 (M+). Waters Xbridge C18, 19×150 mm, 5 μm; Guard Column: WatersXBridge C18, 19×10 mm, 5 μm; Mobile Phase A: 5:95 Acetonitrile:waterwith 10 mM NH₄OAc; Mobile Phase B: 95:5 acetonitrile:water with 10 mMNH₄OAc; Gradient: 10-50% B over 25 minutes, followed by a 10 minute holdat 50% B and 5 minute hold at 100% B; Flow: 15 mL/min. R_(t) Min: 1.91,Wave length: 220 nm.

Example 471-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one

To a 1 dram vial were added6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(0.035 g, 0.091 mmol), CH₃CN, TEA (0.038 mL, 0.273 mmol), and HATU(0.036 g, 0.091 mmol). The material went into solution and2-((tert-butoxycarbonyl)(methyl)amino)acetic acid (0.034 g, 0.182 mmol)was added. The reaction vial was capped and allowed to stir overnight atroom temperature. After 18 hrs LC-MS showed product had formed. Thesamples were diluted with ethyl acetate and washed with water. Thecombined organics were washed with brine, dried over Na₂SO₄ filtered,and concentrated. To this was added 1 mL of DCM and 1 mL of 4 M HCl indioxane. The reaction mixture was stirred for 30 minutes at roomtemperature, concentrated, diluted with Solvent B (90:10:0.1CH₃CN:Water:TFA, filtered and purified by preparative reverse phasechromatography. The crude material was purified via preparative LC/MSwith the following conditions: Column: XBridge C18, 19×200 mm, 5-μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammoniumacetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammoniumacetate; Gradient: 10-50% B over 20 minutes, then a 5-minute hold at100% B; Flow: 20 mL/min. Fractions containing the product were combinedand dried via centrifugal evaporation. The yield of the product was 7.4mg, and its estimated purity by LCMS analysis was 96%. Two analyticalLC/MS injections were used to determine the final purity. Injection 1conditions: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7 μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammoniumacetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammoniumacetate; Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection: UV at 220 nm.Injection 2 conditions: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm,1.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1%trifluoroacetic acid; Temperature: 50° C.; Gradient: 0-100% B over 3minutes, then a 0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection:UV at 220 nm. Proton NMR was acquired in deuterated DMSO. LC-MS:M+1=431, rt=1.127 min., [D1]. Proton NMR was acquired in deuteratedDMSO. ¹H NMR (500 MHz, DMSO-d₆) δ 11.19 (s, 1H), 8.97 (s, 1H), 8.58 (s,1H), 7.98 (d, J=9.2 Hz, 1H), 7.79 (d, J=10.4 Hz, 1H), 7.56 (s, 1H), 7.33(d, J=8.3 Hz, 1H), 7.03 (d, J=8.8 Hz, 1H), 4.55 (d, J=13.0 Hz, 1H), 3.88(d, J=13.2 Hz, 1H), 3.58 (s, 1H), 3.33-3.21 (m, 1H), 3.16-3.06 (m, 1H),2.88 (d, J=7.5 Hz, 2H), 2.77-2.63 (m, 2H), 2.38 (s, 5H), 1.73-1.59 (m,2H), 1.43 (d, J=7.0 Hz, 6H).

The following examples were prepared according to the general methodsdisclosed in Examples 46 or 47.

TABLE 6 Ex. LCMS R_(t) No. Structure MH⁺ (min) Method 48

415.9 1.62 QC-ACN-AA-XB 49

441.3 1.46 QC-ACN-TFA-XB 50

445.3 1.47 Method A 51

445.1 1.21 QC-ACN-AA-XB 52

446.4 1.57 Method E 53

446.2 1.70 Method E 54

455.3 1.74 QC-ACN-AA-XB 55

456.4 1.85 Method E 56

457.4 1.27 Method F 57

459.5 1.16 QC-ACN-TFA-XB 58

459.4 1.29 Method F 59

459.4 1.29 Method F 60

460.3 1.79 A 61

460.4 1.66 Method F 62

461.3 1.43 Method E 63

462.3 1.52 Method E 64

472.4 1.56 Method E 65

472.4 2.12 Method E 66

473 1.65 QC-ACN-AA-XB 67

475.3 1.50 Method E

Example 681-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-2-morpholinoethan-1-one

6-(3-Isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridinehydrochloride (0.250 g, 0.610 mmol) was dissolved in NMP (5 mL). Et₃N(0.255 mL, 1.829 mmol) and 2-chloroacetyl chloride (0.073 mL, 0.915mmol) were added sequentially. The reaction was monitored by LCMS. Afterstirring for 1.5 hours, the reaction mixture was diluted with NMP andused as a solution in the next step.

2-Chloro-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethanone(0.035 g, 0.078 mmol) was dissolved in NMP (1 mL). DBU (0.059 mL, 0.389mmol) and morpholine (0.020 mL, 0.233 mmol) were added sequentially. Thereaction was monitored by LCMS. The reaction mixture was stirredovernight. The reaction mixture was diluted with solvent (90:10 ACN:water, 0.1% TFA) and the crude material was purified via preparativeLC/MS with the following conditions: Column: XBridge C18, 19×200 mm,5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile: water with 0.1%trifluoroacetic acid; Gradient: 10-50% B over 30 minutes, then a5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing theproduct were combined and dried via centrifugal evaporation.

The yield of the product was 37.9 mg, and its estimated purity by LCMSanalysis was 100%. Two analytical LC/MS injections were used todetermine the final purity. Injection 1 conditions: Column: WatersAcquity UPLC BEH C18, 2.1×50 mm, 1.7-μm particles; Mobile Phase A: 5:95acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5acetonitrile:water with 10 mM ammonium acetate; Temperature: 50° C.;Gradient: 0-100% B over 3 minutes, then a 0.75-minute hold at 100% B;Flow: 1.0 mL/min; Detection: UV at 220 nm. Injection 2 conditions:Column: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7-μm particles; MobilePhase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; MobilePhase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid;Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection: UV at 220 nm.LC-MS: M+1=501, rt=1.157 min., [D1]. Proton NMR was acquired indeuterated DMSO. ¹H NMR (400 MHz, DMSO-d₆) δ=11.12 (s, 1H), 8.79 (d,J=0.8 Hz, 1H), 8.53 (s, 1H), 7.59 (d, J=6.4 Hz, 2H), 7.29 (d, J=8.4 Hz,1H), 7.02 (dd, J=8.4, 1.2 Hz, 1H), 4.88-4.82 (m, 2H), 4.52-4.48 (m, 1H),4.28-4.22 (m, 2H), 4.09-4.04 (m, 1H), 3.28-3.21 (m, 1H), 3.19-3.02 (m,6H), 2.85-2.76 (m, 1H), 2.68-2.59 (m, 2H), 2.58 (s, 3H), 1.88-1.80 (m,2H), 1.69-1.50 (m, 2H), 1.43 (d, J=7.2 Hz, 6H).

The following examples were prepared according to the general processdisclosed in Example 68.

TABLE 7 Ex. LCMS R_(t) No. Structure MH⁺ (min) Method 69

487.4 1.28 Method F 70

473.4 1.35 Method E 71

489.4 1.40 Method E 72

473.4 1.39 Method E 73

487.4 1.25 Method F

Example 741-(1,1-dioxido-1,2,4-thiadiazinan-4-yl)-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)ethan-1-one

Intermediate 74A:2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)aceticacid

In a glass vial,6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.580 g, 1.233 mmol) was dissolved in CH₂Cl₂ (8.22 mL) andN,N-diisopropylethylamine (1.074 mL, 6.16 mmol). Methyl 2-bromoacetate(0.141 mL, 1.479 mmol) was added to the vial, resulting in a clear,bright yellow solution. The reaction mixture was stirred for 1.5 h atroom temperature. Excess solvent was evaporated from the reactionmixture under a nitrogen stream. The material was purified by silica gelchromatography using hexane and ethyl acetate as eluents (0%-100% Ethylacetate gradient). The product fractions were combined and evaporated todryness. The material was dissolved in 2 mL THF and 2 mL MeOH andtreated with 2 mL of 4 M NaOH. Next, 1 mL of water was added and themixture was stirred at 45° C. overnight. The mixture was diluted withwater and acidified to pH=5 with 1 N HCl. Ethyl acetate was added andthe layers were separated. The combined organics were washed with driedover Na₂SO₄, filtered and concentrated to afford2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)acetic acid.

Example 74

In a 2 dram vial were added2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)aceticacid (0.025 g, 0.058 mmol), CH₃CN and TEA (0.024 mL, 0.174 mmol). Thesample went into solution and HATU (0.033 g, 0.087 mmol) was added. Thereaction vial was capped and allowed to stir overnight at roomtemperature. The sample was diluted with solvent (90:10:0.1CH₃CN:water:TFA), filtered and then purified by preparative reversephase HPLC.

The crude material was purified via preparative LC/MS with the followingconditions: Column: XBridge Phenyl, 19×200 mm, 5-μm particles; MobilePhase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; MobilePhase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient:20-60% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20mL/min. Fractions containing the product were combined and dried viacentrifugal evaporation. The yield of the product was 0.8 mg and itsestimated purity by LCMS analysis was 99%. Two analytical LC/MSinjections were used to determine the final purity. Injection 1conditions: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm, 1.7-μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammoniumacetate; Mobile Phase B: 95:5 acetonitrile: water with 10 mM ammoniumacetate; Temperature: 50° C.; Gradient: 0-100% B over 3 minutes, then a0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection: UV at 220 nm.Injection 2 conditions: Column: Waters Acquity UPLC BEH C18, 2.1×50 mm,1.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1%trifluoroacetic acid; Temperature: 50° C.; Gradient: 0-100% B over 3minutes, then a 0.75-minute hold at 100% B; Flow: 1.0 mL/min; Detection:UV at 220 nm. Proton NMR was acquired in deuterated DMSO.

The following examples were prepared according to the general processdescribed in Example 74.

TABLE 8 Ex. LCMS R_(t) No. Structure MH⁺ (min) Method 75

471.4 1.72 Method E 76

473.4 1.56 Method E 77

515.4 1.40 Method E 78

485.4 1.25 Method F 79

513.4 1.08 Method F 80

487.4 1.29 Method F 81

473.4 1.83 Method E 82

515.4 1.10 Method F 83

501.4 1.06 Method F 84

501.4 1.05 Method F 85

558.5 0.96 Method F 86

471.4 1.13 Method F 87

473.4 1.23 Method F 88

501.4 1.11 Method F 89

499.4 1.3 Method F 90

485.4 1.59 Method E 91

549.4 1.52 Method E 92

501.4 1.66 Method E 93

485.4 1.58 Method E

Example 948-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 94A: 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine(100 mg, 0.309 mmol) in EtOH (20 mL) was added vinylboronic acid pinacolester (62.0 mg, 0.463 mmol). The mixture was degassed for 10 min usingN₂. Next, PdCl₂(dppf)-CH₂Cl₂ (12.61 mg, 0.015 mmol) and Et₃N (0.129 mL,0.926 mmol) were added and the reaction mixture was heated to 80° C. for16 h. The reaction mixture was filtered through pad of celite, washedwith EtOAc, and concentrated organic layer to afford6-bromo-8-vinyl-[1,2,4]triazolo[1,5-a]pyridine (70 mg, 95%). LCretention time 1.0.4 min [K]. MS (E−) m/z: 226 (M+H).

Intermediate 94B: tert-butyl4-(3-isopropyl-2-(8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

To a stirred solution of tert-butyl4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(300 mg, 0.640 mmol), and 6-bromo-8-vinyl-[1,2,4]triazolo[1,5-a]pyridine(215 mg, 0.961 mmol) in dioxane (15 mL) and water (2 mL) was addedpotassium phosphate tribasic (408 mg, 1.921 mmol). The mixture wasdegassed with N₂ for 10 min. Next, PdCl₂(dppf) (46.9 mg, 0.064 mmol) wasadded the mixture was degassed for 10 min. The reaction mixture washeated 80° C. for 16 h. The reaction mass was filtered through pad ofcelite, washed with EtOAc, and concentrated to afford tert-butyl4-(3-isopropyl-2-(8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate. The crude mass was purified by silica gelchromatography to afford tert-butyl4-(3-isopropyl-2-(8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(230 mg, 74%) as white solid. LC retention time 1.74 min [K]. MS (E−)m/z: 486 (M+H).

Intermediate 94C: tert-butyl4-(2-(8-ethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

A solution oftert-butyl-4-(3-isopropyl-2-(8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(180 mg, 0.371 mmol) in ethyl acetate (15 mL) was purged with nitrogen(N₂). Palladium on carbon (39.4 mg, 0.371 mmol)) was added and themixture was purged with N₂ three times. Hydrogen gas (H₂) was introducedvia a balloon to the mixture. The reaction mixture was stirred at roomtemperature for 5 h. The suspension was filtered through celite, thefiltrate was collected and concentrated to afford crude compound. Thecrude was purified by silica gel chromatography. The compound was elutedin 15% ethyl acetate in hexane, the fractions were collected andconcentrated to afford to afford tert-butyl4-(2-(8-ethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(150 mg, 83% yield) as a white solid. LCMS retention time 1.70 min [K].MS (E−) m/z: 488 (M+H).

Example 94

To a solution of tert-butyl4-(2-(8-ethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(140 mg, 0.287 mmol) in DCM (10 mL) was added 4 M HCl in dioxane (3.05μl, 0.100 mmol at ambient temperature. The mixture was stirred at thesame temperature for 1 h. The solution was concentrated to afford crudeproduct. The crude material was purified by prep LCMS with the followingconditions: Waters Xbridge C18, 19×150 mm, 5 μm; Guard Column: WatersXBridge C18, 19×10 mm, 5 μm; Mobile Phase A: 5:95 methanol:water with 10mM NH₄OAc; Mobile Phase B: 95:5 methanol:water with 10 mM NH₄OAc;Gradient: 15-65% B over 25 minutes, followed by a 10 minute hold at 65%B and 5 minute hold at 100% B; Flow: 15 mL/min. Fractions containing theproduct were combined and dried using a Genevac centrifugal evaporatorto provide8-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(5.4 mg, 8.5%) as a white solid. LC retention time=1.38 min [E]. MS (E−)m/z: 388 (M+H).

Example 958-isopropyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 95A:6-bromo-8-(prop-1-en-2-yl)-[1,2,4]triazolo[1,5-a]pyridine

To a stirred solution of 6-bromo-8-iodo-[1,2,4]triazolo[1,5-a]pyridine(300 mg, 0.926 mmol) and4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (202 mg,1.204 mmol) in dioxane (10 mL) and water (0.5 mL) was added potassiumphosphate tribasic (590 mg, 2.78 mmol). The reaction mixture wasdegassed with N₂ for 10 min. Next, PdCl₂(dppf) (67.8 mg, 0.093 mmol) wasadded and the reaction mixture was degassed for 10 min. The reactionmixture was heated to 80° C. for 16 h. The reaction mass was filteredthrough a pad of celite, washed with EtOAc, and concentrated. The crudemass was purified by silica gel chromatography using 60% EtOAc-hexanesto afford (6-bromo-8-(prop-1-en-2-yl)-[1,2,4]triazolo [1,5-a]pyridine(200 mg, 0.840 mmol, 91% yield) as an off-white solid. LC retention time1.19 min [K]. MS (E−) m/z: 240 (M+H).

Intermediate 95B: tert-butyl4-(3-isopropyl-2-(8-(prop-1-en-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

To a stirred solution of tert-butyl4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(300 mg, 0.640 mmol),6-bromo-8-(prop-1-en-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (229 mg, 0.961mmol) in dioxane (15 mL), and water (2 mL) was added potassium phosphatetribasic (408 mg, 1.921 mmol) degassed with N₂ for 10 mins, thenPdCl₂(dppf) (46.9 mg, 0.064 mmol) was added. The reaction mixture washeated 100° C. for 16 h. Reaction mass filtered through celite bedwashed with EtOAc and concentrated to afford crude material. Thismaterial was purified by silica gel chromatography to afford tert-butyl4-(3-isopropyl-2-(8-(prop-1-en-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate.The crude mass was purified by ISCO silica column to afford tert-butyl4-(3-isopropyl-2-(8-(prop-1-en-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(260 mg, 81% yield) as a brown liquid. LC retention time 1.87 min [K].MS (E−) m/z: 500 (M+H).

Intermediate 95C: tert-butyl4-(3-isopropyl-2-(8-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

A solution of tert-butyl4-(3-isopropyl-2-(8-(prop-1-en-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(180 mg, 0.360 mmol) in ethyl acetate (15 mL), was purged with nitrogen(N₂). Next, palladium on carbon (38.3 mg, 0.360 mmol) was added and themixture was purged with N₂ three times. Hydrogen gas (H₂) was introducedvia a balloon to the mixture. The reaction mixture was stirred at roomtemperature for 5 h. The suspension was filtered through celite and thefiltrate was collected and concentrated to afford the crude compound.The crude material was purified by silica gel chromatography and thecompound eluted in 15% ethyl acetate in hexane. The fractions werecollected and concentrated to afford tert-butyl4-(3-isopropyl-2-(8-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(160 mg, 89% yield). LCMS retention time 1.81 min [K]. MS (E−) m/z: 502(M+H).

Example 95

To a solution of tert-butyl4-(3-isopropyl-2-(8-isopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(140 mg, 0.279 mmol) in DCM (10 mL) was added 4 M HCl in dioxane (5 mL)at ambient temperature. The mixture was stirred at the same temperaturefor 1 h. The solution was concentrated to afford crude product. Thecrude sample was purified by preparative LCMS with the followingconditions: Waters Xbridge C18, 19×150 mm, 5 m; Guard Column: WatersXBridge C18, 19×10 mm, 5 μm; Mobile Phase A: 5:95 Methanol:water with 10mM NH₄OAc; Mobile Phase B: 95:5 Methanol:water with 10 mM NH₄OAc;Gradient: 15-65% B over 25 minutes, followed by a 10 minute hold at 65%B and 5 minute hold at 100% B; Flow: 15 mL/min. Fractions containing theproduct were combined and dried using a Genevac centrifugal evaporatorto provide8-isopropyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(1.5 mg, 1.3%) as a white solid. LC retention time=1.49 min [E]. MS (E⁻)m/z: 402 (M+H).

Example 968-chloro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 96A: tert-butyl4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

A solution of tert-butyl4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(2.0 g, 4.27 mmol),6-bromo-8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine (1.158 g, 4.70mmol) and potassium phosphate, tribasic (2.231 g, 12.81 mmol) in dioxane(60 mL) and water (4 mL) was degassed with N₂ for 10 min. Next,PdCl₂(dppf)-CH₂Cl₂ adduct (0.174 g, 0.213 mmol) was added and themixture was degassed for 5 min. The resulting reaction mixture washeated at 90° C. for 12 h. The reaction mixture was concentrated. Theresidue was dissolved in ethyl acetate and the solution was washed withwater. The organic layer was collected, dried over Na₂SO₄ andconcentrated to afford crude compound. The residue was taken up in DCM(1 mL) and recrystallized with pet ether (3×10 mL). The brown solidformed was filtered and dried to afford tert-butyl4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(1.4 g, 2.76 mmol, 64.5%) as a pale yellow solid. LCMS retention time3.74 min [D]. MS (E⁻) m/z: 508.3 (M+H).

Example 96

To a stirred solution of tert-butyl4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(250 mg, 0.492 mmol) in CH₂Cl₂ (2 mL) was added TFA (0.2 mL) at roomtemperature. The reaction mixture was stirred at the same temperature 2h. The reaction mass was concentrated to afford crude compound. Thecrude material was purified via preparative LC/MS with the followingconditions: Column: Waters XBridge C18, 19×150 mm, 5-μm particles;Mobile Phase A: 0.1% trifluoroacetic acid; Mobile Phase B: acetonitrile;Gradient: 10-35% B over 25 minutes, then a 5-minute hold at 100% B;Flow: 15 mL/min. Fractions containing the product were combined anddried via centrifugal evaporation to afford8-chloro-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.200 g, 99% yield) as a pale solid. LC retention time=2.31 min [E]. MS(E⁻) m/z: 409.4 (M+H). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.32-1.52 (m, 7H)1.80-1.96 (m, 3H) 2.07 (s, 1H) 2.28-2.40 (m, 1H) 2.61-2.72 (m, 1H)2.88-3.04 (m, 2H) 3.17 (d, J=5.02 Hz, 2H) 3.21-3.28 (m, 2H) 4.10 (q,J=5.02 Hz, 1H) 7.02 (dd, J=8.53, 1.51 Hz, 1H) 7.35 (d, J=8.03 Hz, 1H)7.57 (s, 1H), 8.02 (d, J=1.51 Hz, 1H) 8.77-8.94 (m, 1H) 11.24 (s, 1H).

Example 978-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 97A: tert-butyl4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

A solution of tert-butyl4-(2-(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(0.1 mg, 0.197 μmol), ethylboronic acid (0.015 mg, 0.197 μmol), andpotassium phosphate, dibasic (0.086 mg, 0.492 μmol) in toluene (2 mL)and water (0.5 mL) was degassed with N₂ for 10 min. Next, Pd(OAc)₂ (4.42μg, 0.020 μmol) and tricyclohexylphosphine (2.76 μg, 0.0098 μmol) wereadded and the reaction mixture was degassed for 5 min. The reactionmixture was heated at 100° C. for 12 h. The reaction mixture wasconcentrated. The residue was dissolved in ethyl acetate and thesolution was washed with water. The organic layer was collected, driedover Na₂SO₄, and concentrated to afford tert-butyl4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (80 mg, 1.59 mmol, 81%) as a pale yellow solid.LCMS retention time 3.93 min [D]. MS (E⁻) m/z: 502.3 (M+H).

Example 97

To a solution of tert-butyl4-(2-(8-ethyl-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(0.08 g, 0.159 mmol) in DCM (2 mL) was added 4 M HCl in dioxane (0.399mL, 1.595 mmol) drop wise. The reaction mixture was stirred at 25° C.for 1 h. The reaction mass was concentrated to afford crude compound.The crude material was purified via preparative LC/MS with the followingconditions: Column: Waters XBridge C18, 19×150 mm, 5-μm particles;Mobile Phase A: 10-mM ammonium acetate; Mobile Phase B: acetonitrile;Gradient: 8-38% B over 25 minutes, then a 5-minute hold at 100% B; Flow:15 mL/min. Fractions containing the product were combined and dried viacentrifugal evaporation to afford8-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-2-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.0013 g, 2% yield) as a pale solid. LC retention time=1.369 min [D1].MS (E⁻) m/z: 402 (M+H). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 11.17 (s, 1H),8.69 (s, 1H), 7.54 (d, J=18.6 Hz, 2H), 7.41-7.30 (m, 1H), 7.01 (d, J=9.0Hz, 1H), 3.19-3.16 (m, 5H), (3.08-2.95 (m, 8H), 2.08 (s, 1H), 1.99 (d,J=13.2 Hz, 6H), 1.87 (d, J=12.2 Hz, 7H), 1.45 (d, J=7.1 Hz, 9H),1.40-1.34 (m, 3H).

Example 98 tert-butyl4-(2-(8-ethyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

Intermediate 98A:6-bromo-7-methyl-8-vinyl-[1,2,4]triazolo[1,5-a]pyridine

A solution of 6-bromo-8-iodo-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.25 g, 0.740 mmol) and potassium vinyltrifluoroborate (0.099 g, 0.740mmol) in ethanol (5 mL) was degassed with N₂ for 10 min. Next,PdCl₂(dppf)-CH₂Cl₂ adduct (0.030 g, 0.037 mmol) was added and thereaction mixture was degassed for 5 min followed by the addition of TEA(0.412 mL, 2.96 mmol). The resulting reaction mixture was heated at 85°C. for 12 h. The reaction mixture was concentrated. The residue wasdissolved in ethyl acetate and the solution was washed with water. Theorganic layer was collected, dried over Na₂SO₄, and concentrated toafford 6-bromo-7-methyl-8-vinyl-[1,2,4]triazolo[1,5-a]pyridine (0.25 g,0.473 mmol, 63.9% yield) as a yellow solid. LCMS retention time 1.42 min[H]. MS (E⁻) m/z: 240.3 (M+2H).

Intermediate 98B: tert-butyl4-(3-isopropyl-2-(7-methyl-8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

A solution of tert-butyl4-(3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.4 g, 0.854 mmol),6-bromo-7-methyl-8-vinyl-[1,2,4]triazolo[1,5-a]pyridine (0.224 g, 0.939mmol), and potassium phosphate tribasic (0.446 g, 2.56 mmol) in dioxane(5 mL) and water (1 mL) was degassed with N₂ for 10 min. Next,PdCl₂(dppf)-CH₂Cl₂ adduct (0.035 g, 0.043 mmol) was added and themixture was again degassed for 5 min. The resulting reaction mixture washeated at 90° C. for 12 h. The reaction mixture was concentrated. Theresidue was dissolved in ethyl acetate and the solution was washed withwater. The organic layer was collected, dried over Na₂SO₄, andconcentrated to afford crude compound. The residue was taken up in DCM(1 mL) and recrystallized with pet ether (3×10 mL). The crude materialwas purified by combiflash 5% MeOH/CHCl₃. Concentration of fractionsprovided tert-butyl4-(3-isopropyl-2-(7-methyl-8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.35 g, 0.700 mmol, 82%) as a yellow solid. LCMS retention time 3.11min [D]. MS (E−) m/z: 500.3 (M+H).

Intermediate 98C: tert-butyl4-(2-(8-ethyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

A solution of tert-butyl4-(3-isopropyl-2-(7-methyl-8-vinyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.35 g, 0.700 mmol) in methanol (10 mL) was purged with nitrogen (N₂).Next, Pd/C (0.019 g, 0.018 mmol) was added and the mixture was purgedwith N₂ three times. Hydrogen gas (H₂) was introduced via a balloon tothe mixture. The reaction mixture was stirred at room temperature for 5h. The suspension was filtered through celite bed, the filtrate wascollected, and concentrated to afford tert-butyl4-(2-(8-ethyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (250 mg, 0.498 mmol, 72%) as a white solid.LCMS retention time 4.45 min [H]. MS (E⁻) m/z: 502.3 (M+H).

Example 98

To a solution of tert-butyl4-(2-(8-ethyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(0.25 g, 0.498 mmol) in DCM (2 mL) was added 4 M HCl in dioxane (0.249mL, 0.997 mmol) drop wise. The reaction mixture was stirred at 25° C.for 1 h. The crude material was purified via preparative LC/MS with thefollowing conditions: Column: Waters XBridge C18, 19×150 mm, 5-μmparticles; Mobile Phase A: 10-mM ammonium acetate; Mobile Phase B:methanol; Gradient: 20-60% B over 20 minutes, then a 5-minute hold at100% B; Flow: 15 mL/min. Fractions containing the product were combinedand dried via centrifugal evaporation to afford8-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(180 mg, 90%) as a pale solid. LCMS retention time 1.368 min [E]. MS(E⁻) m/z: 402.2 (M+H).

The following examples were prepared according to the general proceduresdisclosed in Examples 1 and 2.

TABLE 9 Fragment Ex. Starting LCMS R_(t) No. Material Structure MH⁺(min) HPLC Method 99 F-17

418.2 1.33 QC-AC-N-AA-XB 100 F-10

417.9 1.18 QC-ACN-AA-XB 101 F-12

418.0 0.65 A1 102 F-14

392.0 1.2 QC-ACN-AA-XB 103 F-9

403.9 1.14 QC-ACN-TFA-XB 104 F-11

404.2 0.99 QC-ACN-AA-XB 105 F-13

399.1 1.21 QC-ACN-AA-XB 106 F-14

392.0 1.2 QC-ACN-TFA-XB 107 F-14

392.0 1.42 QC-ACN-AA-XB 108 F-8

389.9 0.88 QC-ACN-AA-XB 109 F-58

361.3 0.71 QC-ACN-AA-XB 110 F-18

388.2 1.25 QC-ACN-TFA-XB 111 F-19

385.2 1.19 QC-ACN-TFA-XB 112 F-20

378.0 1.148 QC-ACN-AA XB 113 F-8

390.2 0.61 A1 114 F16

420.2 0.61 A1 115 F-7

— 0.63 A1 116 F-16

462.2 0.67 A1 117 F-59

377.2 0.66 TS1

TABLE 10 Fragment Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 118 F-39

395.3 2.01 E 119 F-36

409.1 1.37 E 120 F-40

443.2 1.78 E 121 F-1

346.6 0.81 E 122 F-21

375.3 1.06 E 123 F-22

375.2 1.28 E 124 F-23

389.3 1.22 F 125 F-24

389.2 1.30 F 126 F-25

392.3 1.39 F 127 F-26

391.3 1.13 E 128 F-27

428.2 1.46 F 131 F-28

391.3 0.95 E 132 F-29

405.3 1.16 E 133 F-31

405.2 1.37 E 134 F-32

441.2 1.43 E 135 F-30

419.3 1.39 E 136 F-33

433.4 1.41 E 138 F-34

423.2 1.42 E 140 F-35

405.2 1.36 E 141 F-54

415.1 1.40 F 142 F-21

396.3 0.88 E 143 F-41

446.3 1.37 E 144 F-45

404.2 1.43 F 145 F-46

458.2 1.49 F 146 F-47

448.3 1.32 F 147 F-48

480.2 1.28 F 148 F-49

493.2 1.28 F 149 F-44

459.3 1.07 F 150 F-41

460.3 1.42 F 151 F-52

401.3 1.21 F 152 F-55

414.2 1.36 F 153 F-40

443.2 1.33 E 154 F-57

459.2 1.68 E 155 F-37

389.2 1.15 F 156 F-5

412.2 0.92 E 157 F-5

376.4 1.34 D 158 F-2

360.2 1.40 D 159 F-51

465.3 1.54 N 160

426.2 1.35 N

Example 1616-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 161A: 5-bromo-1-tosyl-1H-indole

To a stirred solution of 5-bromo-1H-indole (5.0 g, 25.5 mmol), TsCl(6.03 g, 31.6 mmol), and tetrabutylammonium hydrogen sulfate (0.63 g,1.855 mmol) in toluene (100 mL) was added NaOH (50% solution in water,10.20 g, 255 mmol) dropwise. The reaction mixture was stirred for 16 hat room temperature. The reaction was quenched with water (20 mL). Thelayers were separated, the aqueous layer was extracted with EtOAc (2×50mL), the combined organic extracts were dried (Na₂SO₄) and concentratedto yield crude material. The crude material was purified by silica gelchromatography. The compound was eluted in 4% EA in hexanes, thefractions was collected and concentrated to afford5-bromo-1-tosyl-1H-indole (7.1 g, 20.27 mmol) as a white solid. LCretention time=2.230 min [A]. MS (E⁻) m/z: 393.3 (M−H).

Intermediate 161B:1-(5-bromo-1-tosyl-1H-indol-3-yl)-2,2-difluoroethan-1-one

To a suspension of AlCl₃ (6.85 g, 51.4 mmol) in DCM (50 mL) was addeddifluoroacetic anhydride (4.47 g, 25.7 mmol). The reaction mixture wasstirred for 15 min, then a solution of 5-bromo-1-tosyl-1H-indole (3 g,8.57 mmol)) in DCM (30 mL) was added. The reaction mixture was stirredfor 1 h at ambient temperature. The reaction was quenched withice-water. The mixture was extracted with DCM (2×50 mL), combinedextracts was washed with aqueous NaHCO₃, brine, dried over MgSO₄,filtered and concentrated to yield crude material. The crude materialwas purified by silica gel chromatography, the compound was eluted in10% EtOAc in hexane, the fraction was collected and concentrated toafford 1-(5-bromo-1-tosyl-1H-indol-3-yl)-2,2-difluoroethanone (2.21 g,4.1 mmol) as a crystalline solid. LC retention time=2.732 min [A]. MS(E⁻) m/z: 428.0 (M+H).

Intermediate 161C: 1-(5-bromo-1H-indol-3-yl)-2,2-difluoroethan-1-one

To a solution of 1-(5-bromo-1-tosyl-1H-indol-3-yl)-2,2-difluoroethanone(0.2 g, 0.467 mmol) in THF (4 mL) and MeOH (4.00 mL) solvent mixture wasadded Cs₂CO₃ (0.45 g, 1.381 mmol) at room temperature. The mixture wasstirred at room temperature for 12 h. The reaction mixture wasconcentrated, the residue was diluted with minimum amount of water andundissolved solids were filtered and dried under vacuum to afford1-(5-bromo-1H-indol-3-yl)-2,2-difluoroethanone (105 mg, 0.244 mmol) as awhite solid. LC retention time=2.233 min [A]. MS (E⁻) m/z: 276 (M+2H).

Intermediate 161D: 5-bromo-3-(2,2-difluoroethyl)-1H-indole

To the stirred solution of1-(5-bromo-1H-indol-3-yl)-2,2-difluoroethanone (0.25 g, 0.912 mmol) inTHF (10 mL) was added BH3DMS (1.368 mL, 2.74 mmol) at 0° C. undernitrogen. The reaction mixture was stirred at 80° C. for 20 h. Thereaction was quenched with water (2 mL) at 0° C. The reaction mixturewas diluted with ethyl acetate (100 mL), washed with sodium bicarbonate(2×25 mL) and water (2×25 mL), combined organic extracts was dried overanhydrous sodium sulphate, filtered and concentrated to yield crudecompound. The crude material was purified on silica gel chromatography,the compound was eluted at 8% ethyl acetate/hexane, the fractions wascollected and concentrated to afford5-bromo-3-(2,2-difluoroethyl)-1H-indole (120 mg, 0.438 mmol) as an oil.LC retention time=2.802 min [D]. MS (E⁻) m/z: 260 (M+H).

Intermediate 161E: tert-butyl4-(3-(2,2-difluoroethyl)-1H-indol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Tert-butyl 4-(3-(2,2-difluoroethyl)-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate was prepared according to the general proceduredescribed in Intermediate T-1B using5-bromo-3-(2,2-difluoroethyl)-1H-indole as the starting intermediate(0.14 g, 80% yield). LC retention time 3.075 min [D]. MS (E⁻) m/z: 361.2(M−H).

Intermediate 161F: tert-butyl4-(3-(2,2-difluoroethyl)-1H-indol-5-yl)piperidine-1-carboxylate

Tert-butyl4-(3-(2,2-difluoroethyl)-1H-indol-5-yl)piperidine-1-carboxylate wasprepared according to the general procedure described in IntermediateT-1C using tert-butyl4-(3-(2,2-difluoroethyl)-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate as the starting intermediate (0.9 g, 88% yield). LCretention time 3.282 min [D]. MS (E⁻) m/z: 265.0 (M+H-Boc).

Intermediate 161G: tert-butyl4-(2-bromo-3-(2,2-difluoroethyl)-1H-indol-5-yl)piperidine-1-carboxylate

Tert-butyl4-(2-bromo-3-(2,2-difluoroethyl)-1H-indol-5-yl)piperidine-1-carboxylatewas prepared according to the general procedure described inIntermediate 194D using tert-butyl4-(3-(2,2-difluoroethyl)-1H-indol-5-yl)piperidine-1-carboxylate as thestarting intermediate (0.3 g, 52% yield). LC retention time 1.10 min[G]. MS (E⁻) m/z: 389.0 (M+2H-tBu).

Intermediate 161H: tert-butyl4-(3-(2,2-difluoroethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate

A mixture of pinacolborane (1.444 g, 11.28 mmol), tert-butyl4-(2-bromo-3-(2,2-difluoroethyl)-1H-indol-5-yl)piperidine-1-carboxylate(1.0 g, 2.256 mmol), bis(benzonitrile) palladium(II) chloride (0.086 g,0.226 mmol), TEA (0.683 g, 6.77 mmol), and2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.092 g, 0.226 mmol) indioxane (20 mL) was degassed with nitrogen for 10 min. The reactionmixture was stirred at 80° C. for 1 h in a sealed tube. The reaction wasquenched with ice cold water. The reaction mixture was diluted withethyl acetate, filtered and washed with excess ethyl acetate, combinedorganic layers was washed with water, brine, dried over sodium sulphateand evaporated to afford crude compound. The crude material was purifiedby silica gel chromatography, the compound was eluted with 25% ethylacetate in hexane, the fractions were collected and concentrated toafford tert-butyl4-(3-(2,2-difluoroethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.650 g, 1.325 mmol, 58.8% yield) as an off-white solid. LC retentiontime 3.282 min [D]. MS (E⁻) m/z: 435.4 (M+H-tBu).

Intermediate 161I: tert-butyl4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

A mixture of tert-butyl4-(3-(2,2-difluoroethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.300, 0.612 mmol), 6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.156 g, 0.734 mmol), PdCl₂(dppf)-CH₂Cl₂ adduct (0.050 g, 0.061 mmol),and tripotassium phosphate (0.390 g, 1.835 mmol) in a solvent mixture ofdioxane (20 mL) and water (2.5 mL) was degassed with nitrogen for 10min. Next, the resulting slurry was stirred at 95° C. for 3 h in asealed tube. The reaction mixture was diluted with ethyl acetate,filtered and washed with excess ethyl acetate, combined organic layerswere washed with water, brine, dried over sodium sulphate and evaporatedto afford crude compound. The crude material was purified by silica gelchromatography, the compound was eluted with 85% ethyl acetate and petether to afford tert-butyl4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.210 g, 0.424 mmol, 69.3% yield) as a light yellow solid. LC retentiontime 1.42 min [G]. MS (E⁻) m/z: 496.4 (M+H).

Example 161

To a solution of tert-butyl4-(3-(2,2-difluoroethyl)-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.210 g, 0.424 mmol) in dioxane (5.0 mL) was added 4 M HCl in dioxane(1.059 mL, 4.24 mmol) at room temperature. The mixture was stirred atthe same temperature for 2 h. The volatiles were evaporated and driedunder vacuum to afford crude compound. The crude material was trituratedwith diethyl ether, dried under vacuum to afford6-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.165 g, 0.417 mmol, 98% yield) as a light yellow solid. LCMS retentiontime 1.021 min [E]. MS (E⁻) m/z: 396.2 (M+H).

Example 1626-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine

Intermediate 162A: tert-butyl4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate

Tert-butyl4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-y1)piperidine-1-carboxylatewas prepared according to the general procedure described forIntermediate 161I using tert-butyl4-(3-(2,2-difluoroethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.250 g, 0.510 mmol). LC retention time 3.102 min [D]. MS (E⁻) m/z:510.2 (M+H).

Example 162

6-(3-(2,2-difluoroethyl)-5-(piperidin-4-yl)-1H-indol-2-yl)-2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridinewas prepared according to the general procedure described in Example 161using tert-butyl4-(3-(2,2-difluoroethyl)-2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboxylate(0.200 g, 0.392 mmol). LC retention time 1.831 min [D]. MS (E⁻) m/z:410.2 (M+H).

The following examples were prepared according to the general proceduresdisclosed in Example 7.

TABLE 11 Template Ex. Starting LCMS R_(t) No. Material Structure MH⁺(min) HPLC Method 163 EX-99

503.2 1.31 QC-ACN-TFA-XB 164 EX-1

445.4 1.31 QC-ACN-AA-XB 165 EX-2

444.4 1.7 QC-ACN-AA-XB 166 EX-2

431.9 1.33 QC-ACN-TFA-XB 167 EX-2

550.9 1.75 QC-ACN-AA-XB 168 EX-2

481.2 1.48 QC-ACN-AA-XB 169 EX-2

484.0 1.85 QC-ACN-AA-XB 170 EX-2

427.1 1.17 QC-ACN-TFA-XB 171 EX-2

453.0 1.97 QC-ACN-AA-XB 172 EX-2

453.0 2.09 QC-ACN-AA-XB 173 EX-2

542.0 2.16 QC-ACN-AA-XB 174 EX-2

495.1 1.58 QC-ACN-AA-XB 175 EX-2

509.0 1.76 QC-ACN-AA-XB 176 EX-2

495.0 1.34 QC-ACN-TFA-XB 177 EX-2

480.1 1.08 QC-ACN-TFA-XB 178 EX-2

495.1 1.25 QC-ACN-AA-XB 179 EX-2

499.4 1.23 QC-ACN-AA-XB 180 EX-3

480.1 1.56 QC-ACN-AA-XB 181 EX-3

412.9 1.84 QC-ACN-AA-XB 182 EX-3

446.0 1.41 QC-ACN-AA-XB 183 EX-3

481.0 0.98 QC-ACN-TFA-XB 184 EX-3

495.0 1.47 QC-ACN-AA-XB 185 EX-3

509.1 1.71 QC-ACN-AA-XB 186 EX-3

453.0 2.19 QC-ACN-AA-XB 187 EX-3

453.3 1.32 QC-ACN-TFA-XB 188 EX-3

427.0 1.73 QC-ACN-AA-XB 189 EX-3

494.9 1.42 QC-ACN-AA-XB 190 EX-3

445.4 1.05 QC-ACN-TFA-XB 191 EX-3

459.4 1.33 QC-ACN-AA-XB 192 EX-3

431.1 1.35 QC-ACN-AA-XB 193 EX-112

463.3 1.27 QC-ACN-TFA-XB 194 EX-112

484.0 1.71 QC-ACN-AA-XB 195 EX-112

417.2 1.88 QC-ACN-AA-XB 196 EX-112

435.1 1.42 QC-ACN-AA-XB 197 EX-112

449.2 1.40 QC-ACN-AA-XB 198 EX-6

489.4 1.44 QC-ACN-AA-XB 199 EX-6

461.1 1.38 QC-ACN-AA-XB 200 EX-6

510.2 1.25 QC-ACN-TFA-XB 201 EX-6

443.0 1.84 QC-ACN-AA-XB 202 EX-6

475.0 1.25 QC-ACN-TFA-XB 203 EX-6

511.3 1.54 QC-ACN-AA-XB 204 EX-4

509.2 1.47 QC-ACN-AA-XB 205 EX-4

523.0 1.73 QC-ACN-AA-XB 206 EX-4

523.0 1.37 QC-ACN-TFA-XB 207 EX-110

473.0 1.35 QC-ACN-TFA-XB 208 EX-110

483.4 1.46 QC-ACN-AA-XB 209 EX-110

494.3 1.65 QC-ACN-AA-XB 210 EX-110

427.35, 425.35 QC-ACN-TFA-XB 211 EX-100

470.9 1.32 QC-ACN-TFA-XB 212 EX-100

457.3 1.33 QC-ACN-TFA-XB 213 EX-100

475.1 1.47 QC-ACN-AA-XB 214 EX-100

524.3 1.63 QC-ACN-AA-XB 215 EX-100

539.0 1.63 QC-ACN-AA-XB 216 EX-100

489.4 1.52 QC-ACN-AA-XB 217 EX-100

503.1 1.3 QC-ACN-TFA-XB 218 EX-100

525.1 1.15 QC-ACN-TFA-XB 219 EX-101

503.2 1.22 QC-ACN-TFA-XB 220 EX-111

506.2 1.24 QC-ACN-AA-XB 221 EX-111

457.0 1.31 QC-ACN-TFA-XB 222 EX-111

491.2 1.66 QC-ACN-AA-XB 223 EX-111

424.3 1.93 QC-ACN-AA-XB 224 EX-111

470.0 1.27 QC-ACN-TFA-XB 225 EX-102

489.4 1.1 QC-ACN-TFA-XB 226 EX-104

489.0 1.18 QC-ACN-AA-XB 227 EX-104

442.9 1.21 QC-ACN-TFA-XB 228 EX-105

484.3 1.43 QC-ACN-AA-XB 229 EX-103

443.0 1.27 QC-ACN-TFA-XB 230 EX-108

429.1 1.16 QC-ACN-TFA-XB 231 EX-113

475.1 1.0 QC-ACN-TFA-XB 232 EX-113

429.2 1.53 QC-ACN-AA-XB 233 EX-113

496.0 1.12 QC-ACN-TFA-XB 234 EX-113

461.3 0.97 QC-ACN-TFA-XB 235 EX-113

471.1 1.63 QC-ACN-TFA-XB 236 EX-114

505.2 1.19 QC-ACN-AA-XB

TABLE 12 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 237 EX-122

445.3 1.76 E 238 EX-122

459.3 1.62 E 239 EX-122

446.3 1.59 E 240 EX-1

431.2 1.71 E 241 EX-1

432.3 1.51 E 242 EX-1

431.2 1.75 E 243 EX-2

499.3 2.1 D 244 EX-124

459.3 1.74 E 245 EX-124

473.3 2.09 D 246 EX-124

460 1.74 E 247 EX-125

473.3 1.56 E 248 EX-125

459.2 1.72 E 249 EX-125

460 1.66 E 250 EX-128

499.3 2.08 E 251 EX-128

513 1.65 E 252 EX-128

500 1.74 E 253 EX-128

467.2 2.26 E 254 EX-128

534.1 2.07 E 255 EX-142

467.2 1.41 E 256 EX-142

481.2 1.26 E 257 EX-155

473 1.65 E 258 EX-155

459 1.83 E 259 EX-153

527.3 1.91 E 260 EX-96

493 1.73 E 261 EX-96

479 1.94 E 262 EX-96

480.3 1.61 E 263 EX-5

496.2 1.81 E 264 EX-5

510.2 5.65 I 265 EX-5

510.1 5.63 I 266 EX-5

448.2 1.87 E 267 EX-131

475.3 1.58 E 268 EX-132

489 1.55 E 269 EX-132

475.3 1.95 E 270 EX-132

476.2 1.76 E 271 EX-133

489.3 1.71 E 272 EX-133

475.3 1.84 E 273 EX-133

476.3 1.7 E 274 EX-134

525.3 1.93 E 275 EX-134

511.3 1.98 E 276 EX-135

503.3 1.84 E 277 EX-135

489.3 2.09 E 278 EX-136

517.2 2.02 E 279 EX-136

503.4 1.93 E 280 EX-118

479 1.68 E 281 EX-118

465 1.85 E 282 EX-118

466 1.74 E 283 EX-137

487.2 1.81 E 284 EX-137

474.1 1.95 E 285 EX-137

473.2 1.98 E 286 EX-119

493.1 1.75 E 287 EX-119

480.1 1.47 E 288 EX-119

479.1 1.91 E 289 EX-119

479.2 1.91 E 290 EX-119

514.2 1.97 E 291 EX-143

516.3 1.88 E 292 EX-143

530.3 1.69 E 293 EX-94

473.3 1.75 E 294 EX-94

459.2 1.95 E 295 EX-95

487.3 1.91 E 296 EX-95

473.3 2.1 E 297 EX-144

474.3 1.97 E 298 EX-145

542.3 1.83 E 299 EX-145

528.3 2.01 E 300 EX-146

532.3 1.62 E 301 EX-146

518.3 1.79 E 302 EX-98

487.3 1.76 E 303 EX-140

475.3 1.9 E 304 EX-140

489.3 1.69 E 305 EX-140

476.3 1.72 E 306 EX-140

510.3 1.72 E 307 EX-147

550.3 1.32 F 308 EX-148

564.3 1.73 E 309 EX-148

578.3 1.56 E 310 EX-149

564.3 1.71 E 311 EX-149

529.3 1.64 E 312 EX-120

527.3 2.17 E 313 EX-120

513.2 2.38 E 314 EX-120

514.2 2.26 E 315 EX-150

544.3 1.72 E 316 EX-150

530.3 1.91 E 317 EX-154

529.2 2.25 E 318 EX-154

543.2 2.08 E 319 EX-151

471.3 1.75 E 320 EX-151

485.3 1.27 F 321 EX-151

506.1 2.03 E 322 EX-151

472.2 1.86 E 323 EX-141

485.2 2.02 E 324 EX-141

486.2 1.89 E 325 EX-141

499.2 1.81 E 326 EX-152

485.1 2.05 E 327 EX-152

499.2 1.86 E 328 EX-152

486.2 1.92 E 329 EX-156

497.3 1.4 E 330 EX-156

483.2 1.55 E 331 EX-157

447.3 1.38 E 332 EX-157

482.3 1.44 E 333 EX-157

433.3 1.28 E 334 EX-157

448.3 1.26 E 335 EX-157

461.3 1.24 E 336 EX-157

434.3 1.22 E 337 EX-158

445.3 1.04 F 338 EX-158

431.3 1.44 E 339 EX-158

466.3 1.5 E 340 EX-158

417.3 1.33 E 341 EX-158

418.3 1.26 E 342 EX-158

432.3 1.31 E 343 EX-161

481.3 1.45 E 344 EX-161

467.2 1.58 E 345 EX-162

495.2 1.53 E 346 EX-162

481.2 1.68 E 347 EX-160

511.3 1.17 E 348 EX-159

550.3 1.97 E 349 EX-156

484.2 1.42 E

The following examples were prepared according to the general procedureof Example 26.

TABLE 13 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 350 EX-1

374.0 1.05 QC-ACN- TFA-XB 351 EX-1

444.4 1.53 QC-ACN- AA-XB 352 EX-1

416.4 1.02 QC-ACN- TFA-XB 353 EX-1

455.2 1.06 QC-ACN- TFA-XB 354 EX-1

444.4 1.17 QC-ACN- TFA-XB 355 EX-1

430.4 1.24 QC-ACN- AA-XB 356 EX-1

404.4 1.09 QC-ACN- AA-XB 357 EX-117

433.2 0.66 TS1 358 EX-1

430.4 1.13 QC-ACN- TFA-XB 359 EX-1

481.9 1.79 QC-ACN- AA-XB 360 EX-1

417.04, 416.86 0.92 QC-ACN- TFA-XB 361 EX-1

455.2 1.89 QC-ACN- AA-XB 362 EX-1

499.2 1.96 QC-ACN- AA-XB 363 EX-1

482.4 1.44 QC-ACN- AA-XB 364 EX-1

468.4 1.15 QC-ACN- TFA-XB 365 EX-1

441.3 1.09 QC-ACN- TFA-XB 366 EX-1

494.2 1.45 QC-ACN- TFA-XB 367 EX-1

455.0 1.31 QC-ACN- AA-XB 368 EX-1

498.4 1.41 QC-ACN- AA-XB 369 EX-1

485.2 1.96 QC-ACN- AA-XB 370 EX-1

469.3 1.85 QC-ACN- AA-XB 371 EX-1

468.4 1.21 QC-ACN- TFA-XB 372 EX-1

469.0 1.54 QC-ACN- AA-XB 373 EX-1

468.0 1.87 QC-ACN- AA-XB 374 EX-1

456.9 1.96 QC-ACN- AA-XB 375 EX-1

482.4 1.42 QC-ACN- AA-XB 376 EX-1

454.0 1.25 QC-ACN- AA-XB 377 EX-1

457.2 1.16 QC-ACN- TFA-XB 378 EX-1

455.4 1.25 QC-ACN- TFA-XB 379 EX-1

440.2 1.14 QC-ACN- TFA-XB 380 EX-1

454.3 1.19 QC-ACN- AA-XB 381 EX-1

454.4 1.32 QC-ACN- AA-XB 382 EX-1

468.4 1.33 QC-ACN- AA-XB 383 EX-1

471.3 2.04 QC-ACN- AA-XB 384 EX-1

221.2 1.45 QC-ACN- AA-XB 385 EX-2

438.2 1.21 QC-ACN- TFA-XB 386 EX-2

469.4 1.2 QC-ACN- TFA-XB 387 EX-2

469.1 1.79 QC-ACN- AA-XB 388 EX-2

418.0 1.16 QC-ACN- AA-XB 389 EX-2

468.2 1.9 QC-ACN- AA-XB 390 EX-2

456.4 1.86 QC-ACN- AA-XB 391 EX-2

432.4 1.19 QC-ACN- AA-XB 392 EX-2

469.2 1.52 QC-ACN- AA-XB 393 EX-2

444.0 1.58 QC-ACN- AA-XB 394 EX-2

458.0 1.58 QC-ACN- AA-XB 395 EX-2

492.1 1.63 QC-ACN- AA-XB 396 EX-2

466.0 1.5 QC-ACN- AA-XB 397 EX-2

446.0 1.1 QC-ACN- TFA-XB 398 EX-2

500.0 2.37 QC-ACN- AA-XB 399 EX-2

482.0 1.31 QC-ACN- AA-XB 400 EX-2

530.0 1.92 QC-ACN- AA-XB 401 EX-2

525.1 2.35 QC-ACN- AA-XB 402 EX-2

466.4 1.72 QC-ACN- AA-XB 403 EX-2

472.4 1.24 QC-ACN- AA-XB 404 EX-2

469.0 1.77 QC-ACN- AA-XB 405 EX-2

482.0 1.96 QC-ACN- AA-XB 406 EX-2

471.0 1.6 QC-ACN- AA-XB 407 EX-2

485.3 1.99 QC-ACN- AA-XB 408 EX-2

471.0 2.18 QC-ACN- AA-XB 409 EX-2

468.0 1.4 QC-ACN- AA-XB 410 EX-2

482.2 1.52 QC-ACN- AA-XB 411 EX-2

472.1 1.36 QC-ACN- TFA-XB 412 EX-2

466.4 1.28 QC-ACN- TFA-XB 413 EX-2

496.4 1.38 QC-ACN- AA-XB 414 EX-2

480.0 1.76 QC-ACN- AA-XB 415 EX-2

480.2 1.77 QC-ACN- AA-XB 416 EX-2

481.0 1.32 QC-ACN- TFA-XB 417 EX-2

481.0 1.32 QC-ACN- TFA-XB 418 EX-2

493.9 1.69 QC-ACN- AA-XB 419 EX-2

482.4 1.26 QC-ACN- AA-XB 420 EX-2

468.2 1.22 QC-ACN- TFA-XB 421 EX-2

480.5 1.47 QC-ACN- AA-XB 422 EX-2

494.1 1.87 QC-ACN- AA-XB 423 EX-2

441.0 1.36 QC-ACN- TFA-XB 424 EX-2

480.0 1.83 QC-ACN- AA-XB 425 EX-2

474.1 1.67 QC-ACN- AA-XB 426 EX-2

484.1 1.15 QC-ACN- AA-XB 427 EX-2

551.1 2.25 QC-ACN- AA-XB 428 EX-2

536.5 1.53 QC-ACN- TFA-XB 429 EX-2

466.3 1.25 QC-ACN- TFA-XB 430 EX-2

565.4 1.89 QC-ACN- AA-XB 431 EX-2

563.4 2.17 QC-ACN- AA-XB 432 EX-2

476.3 1.25 QC-ACN- AA-XB 433 EX-2

470.3 1.92 QC-ACN- AA-XB 434 EX-2

469.2 1.27 QC-ACN- TFA-XB 435 EX-2

469.2 1.9 QC-ACN- AA-XB 436 EX-2

471.1 1.93 QC-ACN- AA-XB 437 EX-2

468.2 1.49 QC-ACN- AA-XB 438 EX-2

526.2 1.54 QC-ACN- TFA-XB 439 EX-2

496.2 1.34 QC-ACN- TFA-XB 440 EX-2

455.2 1.28 QC-ACN- TFA-XB 441 EX-3

430.4 1.66 QC-ACN- AA-XB 442 EX-3

496.2 1.08 QC-ACN- TFA-XB 443 EX-3

458.2 1.05 QC-ACN- TFA-XB 444 EX-3

468.4 1.81 QC-ACN- AA-XB 445 EX-3

468.3 1.1 QC-ACN- TFA-XB 446 EX-3

455.4 1.78 QC-ACN- AA-XB 447 EX-3

469.3 0.98 QC-ACN- TFA-XB 448 EX-3

454.0 1.3 QC-ACN- AA-XB 449 EX-3

469.4 1.33 QC-ACN- AA-XB 450 EX-3

471.0 1.79 QC-ACN- AA-XB 451 EX-3

455.0 1.5 QC-ACN- AA-XB 452 EX-3

465.9 1.69 QC-ACN- AA-XB 453 EX-3

469.0 1.95 QC-ACN- AA-XB 454 EX-3

466.2 1.46 QC-ACN- AA-XB 455 EX-3

506.0 1.69 QC-ACN- AA-XB 456 EX-3

526.0 2.05 QC-ACN- AA-XB 457 EX-3

469.1 1.42 QC-ACN- AA-XB 458 EX-3

456.2 1.77 QC-ACN- AA-XB 459 EX-3

455.4 1.05 QC-ACN- TFA-XB 460 EX-3

492.4 1.21 QC-ACN- TFA-XB 461 EX-3

466.1 1 QC-ACN- TFA-XB 462 EX-3

441.0 1.84 QC-ACN- AA-XB 463 EX-3

480.1 1.05 QC-ACN- TFA-XB 464 EX-3

494.1 1.73 QC-ACN- AA-XB 465 EX-3

480.4 1.71 QC-ACN- AA-XB 466 EX-3

480.0 1.33 QC-ACN- TFA-XB 467 EX-3

466.0 1.85 QC-ACN- AA-XB 468 EX-112

473.0 1.31 QC-ACN- TFA-XB 469 EX-112

434.1 1.18 QC-ACN- TFA-XB 470 EX-6

499.1 1.37 QC-ACN- AA-XB 471 EX-6

510.1 1.75 QC-ACN- AA-XB 472 EX-6

488.1 1.74 QC-ACN- AA-XB 473 EX-6

460.1 1.65 QC-ACN- AA-XB 474 EX-6

551.0 1.69 QC-ACN- AA-XB 475 EX-4

535.4 1.43 QC-ACN- AA-XB 476 EX-4

497.4 1.94 QC-ACN- TFA-XB 477 EX-4

515.0 1.29 QC-ACN- TFA-XB 478 EX-4

444.1 1.74 QC-ACN- AA-XB 479 EX-4

458.4 1.58 QC-ACN- TFA-XB 480 EX-4

416.1 1.32 QC-ACN- AA-XB 481 EX-4

430.0 1.62 QC-ACN- AA-XB 482 EX-4

416.1 1.54 QC-ACN- TFA-XB 483 EX-4

485.2 1.44 QC-ACN- AA-XB 484 EX-4

484.3 2.29 QC-ACN- AA-XB 485 EX-4

402.2 1.29 QC-ACN- AA-XB 486 EX-4

446.2 1.38 QC-ACN- AA-XB 487 EX-110

444.3 1.77 QC-ACN- AA-XB 488 EX-110

471.9 1.28 QC-ACN- AA-XB 489 EX-110

520.4 1.23 QC-ACN- TFA-XB 490 EX-100

524.2 1.8 QC-ACN- AA-XB 491 EX-100

512.2 1.53 QC-ACN- AA-XB 492 EX-100

474.4 1.15 QC-ACN- TFA-XB 493 EX-100

502.1 1.35 QC-ACN- AA-XB 494 EX-100

510.4 1.22 QC-ACN- TFA-XB 495 EX-100

513.4 1.15 QC-ACN- TFA-XB 496 EX-100

550.1 1.46 QC-ACN- AA-XB 497 EX-100

499.1 1.38 QC-ACN- AA-XB 498 EX-100

565.3 1.38 QC-ACN- AA-XB 499 EX-101

474.1 1.09 QC-ACN- TFA-XB 500 EX-111

469.2 1.42 QC-ACN- AA-XB 501 EX-111

441.2 1.18 QC-ACN- TFA-XB 502 EX-102

499.3 1.08 QC-ACN- TFA-XB 503 EX-102

460.3 1.06 QC-ACN- TFA-XB 504 EX-104

460.2 1.49 QC-ACN- AA-XB 505 EX-104

485.3 0.97 QC-ACN- TFA-XB 506 EX-105

483.2 1.26 QC-ACN- TFA-XB 507 EX-107

447.9 1.35 QC-ACN- AA-XB 508 EX-108

446.3 1.53 QC-ACN- AA-XB 509 EX-108

485.1 0.92 QC-ACN- TFA-XB 510 EX-113

446.0 1.39 QC-ACN- AA-XB 511 EX-113

485.3 1.16 QC-ACN- AA-XB 512 EX-113

496.4 1.04 QC-ACN- TFA-XB 513 EX-113

471.1 1 QC-ACN- TFA-XB 514 EX-113

522.4 1.34 QC-ACN- AA-XB 515 EX-113

512.4 1.56 QC-ACN- AA-XB 516 EX-113

484.1 1.27 QC-ACN- AA-XB 517 EX-113

482.1 1.45 QC-ACN- AA-XB 518 EX-113

488.0 1.26 QC-ACN- TFA-XB 519 EX-113

496.4 1.55 QC-ACN- AA-XB 520 EX-113

482.1 1.31 QC-ACN- AA-XB 521 EX-113

474.3 1.03 QC-ACN- TFA-XB 522 EX-113

486.1 1.46 QC-ACN- AA-XB 523 EX-113

485.2 1.01 QC-ACN- TFA-XB 524 EX-113

496.0 1.39 QC-ACN- AA-XB 525 EX-114

460.3 1.44 QC-ACN- AA-XB 526 EX-114

510.0 1.48 QC-ACN- AA-XB 527 EX-114

499.3 1.02 QC-ACN- TFA-XB 528 EX-116

518.0 1.71 QC-ACN- AA-XB 529 EX-116

475.9 1.11 QC-ACN- TFA-XB 530 EX-116

476.0 1.3 QC-ACN- AA-XB

TABLE 14 Fragment Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 531 EX-122

431.3 0.93 E 532 EX-122

467.3 1.56 E 533 EX-122

416.3 1.48 E 534 EX-122

430.3 1.8 E 535 EX-122

458.3 1.45 E 536 EX-1 

402.3 1.47 E 537 EX-2 

470.2 2.5 E 538 EX-2 

543 2.12 E 539 EX-2 

500 2.11 E 540 EX-2 

444.2 1.71 E 541 EX-2 

444.2 1.72 E 542 EX-124

444.3 1.74 E 543 EX-124

473.3 1.71 E 544 EX-124

444 1.82 E 545 EX-124

520.3 1.93 E 546 EX-125

472.3 1.56 E 547 EX-125

444.4 1.69 E 548 EX-125

520 1.58 E 549 EX-128

484 2.03 E 550 EX-128

560 1.88 E 551 EX-128

470 1.56 E 552 EX-128

512 2.5 D 553 EX-128

484.2 2.24 E 554 EX-128

512.1 2.13 E 555 EX-128

512.3 2.15 E 556 EX-128

498.2 1.51 F 557 EX-128

498.2 2.03 E 558 EX-155

444.3 1.65 E 559 EX-155

430.3 1.53 E 560 EX-155

482.3 1.5 E 561 EX-5 

522.4 1.51 E 562 EX-5 

502.3 1.71 E 563 EX-5 

502.2 6.03 I 564 EX-5 

502.4 6.06 I 565 EX-5 

489.3 1.55 E 566 EX-5 

474.3 1.86 E 567 EX-5 

469.2 1.89 E 568 EX-5 

460.2 1.87 D 569 EX-5 

460.1 1.73 E 570 EX-5 

447.1 1.44 E 571 EX-132

488 1.66 E 572 EX-132

460.1 1.34 F 573 EX-132

536 1.9 E 574 EX-133

460.2 1.94 E 575 EX-133

474.2 1.92 D 576 EX-133

474.2 1.94 D 577 EX-137

486.2 1.8 E 578 EX-137

458.3 1.96 E 579 EX-119

492.2 1.7 E 580 EX-119

464.2 2.1 E 581 EX-143

501.3 2.01 E 582 EX-94 

444.3 2.07 E 583 EX-94 

444.3 2.08 E 584 EX-95 

458.3 2.25 E 585 EX-95 

458.2 2.24 E 586 EX-145

513.2 2.15 E 587 EX-98 

458.3 2.11 E 588 EX-140

460.2 2.04 E 589 EX-140

488.3 2.05 E 590 EX-147

535.2 1.32 F 591 EX-148

549.2 1.87 E 592 EX-149

514.3 1.76 E 593 EX-151

456.3 1.88 E 594 EX-141

470.3 1.92 E 595 EX-152

470.1 2.21 E 596 EX-158

416.3 1.54 E 597 EX-161

452.2 1.67 E 598 EX-156

468.2 1.67 E 599 EX-124

430.3 1.49 E 600 EX-157

432.3 1.49 E

The following examples were prepared according to the general methodsdisclosed in Examples 46 and 47.

TABLE 15 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 601 EX-1 

484.9 1.43 QC-ACN-AA-XB 602 EX-2 

535.2 1.95 QC-ACN-AA-XB 603 EX-2 

494.2 1.65 QC-ACN-AA-XB 604 EX-2 

520.3 1.78 QC-ACN-TFA-XB 605 EX-2 

498.0 1.63 QC-ACN-TFA-XB 606 EX-2 

494.2 1.68 QC-ACN-AA-XB 607 EX-2 

509.4 1.66 QC-ACN-AA-XB 608 EX-2 

508.2 1.64 QC-ACN-AA-XB 609 EX-4 

488.0 2.39 QC-ACN-AA-XB 610 EX-4 

529.4 1.63 QC-ACN-AA-XB 611 EX-110

473.4 1.37 QC-ACN-AA-XB

TABLE 16 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 612 EX-122

459.3 2.76 D 613 EX-122

460.3 1.64 E 614 EX-122

474.3 1.83 E 615 EX-122

487.3 1.36 E 616 EX-122

487.3 1.3 E 617 EX-122

460.3 1.67 E 618 EX-122

445.2 1.38 E 619 EX-1 

480.2 1.67 E 620 EX-2 

468.3 1.23 F 621 EX-2 

498.5 2.29 E 622 EX-2 

487.3 1.42 F 623 EX-2 

487.3 1.4 E 624 EX-2 

487.3 1.3 F 625 EX-2 

487 1.4 E 626 EX-2 

501.2 1.46 F 627 EX-2 

489.1 1.74 E 628 EX-2 

529.3 1.5 E 629 EX-124

459.3 1.95 D 630 EX-124

473.3 2.35 D 631 EX-124

474.3 1.85 E 632 EX-124

488.3 1.96 E 633 EX-124

474.3 1.82 E 634 EX-124

601 1.92 E 635 EX-124

501.3 1.36 E 636 EX-124

501.3 1.88 D 637 EX-125

474.3 1.71 E 638 EX-125

473 1.54 E 639 EX-125

459 1.21 E 640 EX-112

463.4 1.06 F 641 EX-128

499.3 1.59 E 642 EX-128

513.3 1.75 E 643 EX-128

500.3 1.83 E 644 EX-128

567.4 1.7 E 645 EX-128

526.4 1.9 E 646 EX-128

514.4 1.88 E 647 EX-128

500.3 1.64 E 648 EX-128

538.3 2.07 E 649 EX-128

527.4 1.48 E 650 EX-128

567.3 1.95 E 651 EX-128

528.2 1.92 E 652 EX-128

500.2 1.77 E 653 EX-128

564.3 2.22 E 654 EX-128

512.3 1.68 E 655 EX-128

555.4 1.82 E 656 EX-142

481.3 1.49 E 657 EX-142

482.2 1.7 E 658 EX-142

496.2 1.72 E 659 EX-142

467.3 1.4 E 660 EX-155

473 1.6 E 661 EX-155

459 1.49 E 662 EX-96 

493.3 1.46 E 663 EX-5 

488.4 1.62 E 664 EX-5 

476.4 1.59 E 665 EX-5 

539.4 1.38 E 666 EX-5 

516.4 1.69 E 667 EX-5 

489.4 1.32 E 668 EX-5 

510.3 1.43 E 669 EX-5 

490.4 1.64 E 670 EX-5 

529.4 1.46 E 671 EX-5 

529.3 1.46 E 672 EX-5 

501.1 1.16 E 673 EX-5 

517.4 1.55 E 674 EX-5 

503.1 1.37 E 675 EX-5 

517.3 1.56 E 676 EX-5 

501.3 1.43 E 677 EX-5 

515.2 7.94 I 678 EX-5 

515.2 7.95 I 679 EX-5 

501.3 1.43 E 680 EX-132

489.1 1.62 E 681 EX-132

475.1 1.48 E 682 EX-133

489.3 1.6 E 683 EX-133

475.3 1.42 E 684 EX-136

517.4 1.65 E 685 EX-118

480.2 1.02 E 686 EX-118

479.2 1.6 E 687 EX-137

487.4 1.64 E 688 EX-137

473.3 1.59 E 689 EX-119

493.1 1.68 E 690 EX-143

530.4 1.4 E 691 EX-148

578.3 1.52 E 692 EX-120

527.3 2.08 E 693 EX-120

513.3 1.93 E 694 EX-120

567.3 1.97 E 695 EX-154

543.2 1.98 E 696 EX-151

485.3 1.5 E 697 EX-151

471.2 1.56 E 698 EX-141

499.2 1.75 E 699 EX-152

499.2 1.77 E 700 EX-152

485.2 1.62 E 701 EX-157

461.3 1.19 E 702 EX-157

447.3 1.08 E 703 EX-158

445.3 1.24 E 704 EX-158

431.3 1.12 E 705 EX-161

482.2 1.57 E 706 EX-161

467.2 1.27 E 707 EX-161

482.2 1.58 E 708 EX-161

495.2 1.48 E 709 EX-161

496.2 1.68 E 710 EX-161

510.3 1.82 E 711 EX-161

481.3 1.37 E 712 EX-161

481.2 1.41 E

The following examples were prepared according to the general processdisclosed in Example 68.

TABLE 17 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 713 EX-1

487.2 1.17 QC-ACN- TFA-XB 714 EX-2

489.1 1.26 QC-ACN- TFA-XB 715 EX-2

515.2 2.36 QC-ACN- AA-XB 716 EX-2

520.9 2.55 QC-ACN- AA-XB 717 EX-2

549.1 2.08 QC-ACN- AA-XB 718 EX-4

561.4 1.46 QC-ACN- TFA-XB 719 EX-4

258.1 1.22 QC-ACN- TFA-XB 720 EX-4

543.1 1.97 QC-ACN- AA-XB 721 EX-4

612.2 1.83 QC-ACN- AA-XB 722 EX-4

543.3 1.78 QC-ACN- AA-XB 723 EX-4

258.4 1.44 QC-ACN- TFA-XB 724 EX-4

556.3 1.2 QC-ACN- TFA-XB 725 EX-4

528.2 1.68 QC-ACN- AA-XB 726 EX-4

512.1 1.87 QC-ACN- AA-XB 727 EX-4

513.2 1.53 QC-ACN- TFA-XB 728 EX-4

527.2 1.77 QC-ACN- AA-XB 729 EX-4

543.3 1.39 QC-ACN- AA-XB 730 EX-4

271.4 1.59 QC-ACN- TFA-XB 731 EX-4

529.3 1.6 QC-ACN- AA-XB 732 EX-4

501.2 1.49 QC-ACN- AA-XB 733 EX-4

515.3 1.84 QC-ACN- AA-XB 734 EX-4

244.2 1.33 QC-ACN- TFA-XB 735 EX-4

515.1 1.41 QC-ACN- TFA-XB 736 EX-4

515.1 1.54 QC-ACN- AA-XB 737 EX-4

487.1 1.54 QC-ACN- AA-XB 738 EX-4

259.4 1.29 QC-ACN- TFA-XB 739 EX-4

246.4 1.24 QC-ACN- TFA-XB 740 EX-4

473.2 1.37 QC-ACN- AA-XB 741 EX-4

549.0 2.01 QC-ACN- AA-XB 742 EX-4

485.1 1.76 QC-ACN- AA-XB 743 EX-4

503.0 1.57 QC-ACN- AA-XB 744 EX-4

513.4 1.73 QC-ACN- AA-XB 745 EX-4

250.3 1.3 QC-ACN- TFA-XB 746 EX-4

501.4 1.41 QC-ACN- TFA-XB 747 EX-4

541.1 2.28 QC-ACN- AA-XB 748 EX-4

502.4 1.37 QC-ACN- TFA-XB 749 EX-4

529.0 1.34 QC-ACN- TFA-XB 750 EX-4

543.1 1.76 QC-ACN- AA-XB 751 EX-4

541.14 541.14 QC-ACN- TFA-XB 752 EX-4

484.4 1.47 QC-ACN- TFA-XB 753 EX-4

459.0 1.4 QC-ACN- AA-XB 754 EX-4

264.4 1.41 QC-ACN- TFA-XB 755 EX-4

529.3 1.46 QC-ACN- AA-XB 756 EX-4

252.3 1.22 QC-ACN- TFA-XB 757 EX-4

489.2 1.28 QC-ACN- AA-XB 758 EX-4

250.3 1.35 QC-ACN- TFA-XB 759 EX-4

544.1 1.64 QC-ACN- AA-XB 760 EX-4

517.5 1.32 QC-ACN- TFA-XB 761 EX-4

527.2 1.86 QC-ACN- AA-XB 762 EX-4

501.1 1.74 QC-ACN- AA-XB 763 EX-4

501.2 1.58 QC-ACN- AA-XB 764 EX-4

499.5 1.37 QC-ACN- TFA-XB 765 EX-4

485.4 1.35 QC-ACN- AA-XB 766 EX-4

487.5 1.32 QC-ACN- TFA-XB 767 EX-4

501.4 1.37 QC-ACN- TFA-XB

TABLE 18 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 768 EX-2 

485.4 1.72 E 769 EX-2 

499.4 1.62 E 770 EX-2 

485.4 1.35 E 771 EX-2 

513.4 1.37 E 772 EX-2 

558.5 1.53 E 773 EX-2 

529.4 1.65 E 774 EX-2 

501.4 1.29 E 775 EX-2 

515.4 1.47 E 776 EX-2 

501.4 1.29 E 777 EX-128

541.4 1.51 F 778 EX-128

527.4 1.44 F 779 EX-128

539.4 2.14 E 780 EX-5 

505.3 1.55 E 781 EX-5 

517.3 1.69 E

The following examples were prepared according to the general processdescribed in Example 74.

TABLE 19 Template Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 782 EX-2

549.2 1.29 QC-ACN- TFA-XB 783 EX-2

535.4 1.31 QC-ACN- TFA-XB 784 EX-2

535.32 1.64 QC-ACN- AA-XB 785 EX-2

505.1 1.77 QC-ACN- AA-XB 786 EX-2

545.2 1.55 QC-ACN- AA-XB 787 EX-2

511.1 1.21 QC-ACN- TFA-XB 788 EX-2

503.2 1.26 QC-ACN- TFA-XB 789 EX-2

517.4 1.35 QC-ACN- TFA-XB 790 EX-2

515.2 1.54 QC-ACN- AA-XB 791 EX-2

529.4 1.58 QC-ACN- AA-XB 792 EX-2

503.2 1.49 QC-ACN- AA-XB 793 EX-2

515.2 1.33 QC-ACN- TFA-XB 794 EX-2

579.2 1.44 QC-ACN- TFA-XB 795 EX-2

531.2 1.22 QC-ACN- AA-XB 796 EX-2

517.2 1.6 QC-ACN- AA-XB 797 EX-2

531.2 1.25 QC-ACN- TFA-XB 798 EX-2

515.2 1.63 QC-ACN- AA-XB 799 EX-2

529.3 1.7 QC-ACN- AA-XB 800 EX-2

545.2 1.56 QC-ACN- TFA-XB 801 EX-2

515.4 1.24 QC-ACN- TFA-XB 802 EX-3

485.0 1.33 QC-ACN- TFA-XB 803 EX-3

473.1 1.76 QC-ACN- AA-XB 804 EX-3

473.0 1.63 QC-ACN- AA-XB 805 EX-3

499.2 1.42 QC-ACN- TFA-XB 806 EX-3

471.4 1.59 QC-ACN- AA-XB 807 EX-3

459.1 1.25 QC-ACN- TFA-XB 808 EX-3

487.4 1.35 QC-ACN- TFA-XB 809 EX-3

501.3 1.5 QC-ACN- AA-XB 810 EX-3

489.3 1.23 QC-ACN- TFA-XB 811 EX-6

528.0 1.46 QC-ACN- AA-XB 812 EX-6

545.0 1.31 QC-ACN- TFA-XB 813 EX-6

580.1 1.58 QC-ACN- AA-XB 814 EX-6

533.2 1.48 QC-ACN- AA-XB 815 EX-6

558.9 1.53 QC-ACN- AA-XB 816 EX-6

489.0 1.63 QC-ACN- AA-XB 817 EX-6

517.0 1.58 QC-ACN- AA-XB 818 EX-6

519.0 1.28 QC-ACN- AA-XB 819 EX-6

503.0 1.44 QC-ACN- TFA-XB 820 EX-6

532.9 1.37 QC-ACN- TFA-XB 821 EX-6

503.0 1.3 QC-ACN- TFA-XB 822 EX-6

575.0 1.39 QC-ACN- AA-XB 823 EX-6

545.0 1.43 QC-ACN- AA-XB 824 EX-6

613.3 1.62 QC-ACN- AA-XB 825 EX-6

533.0 1.4 QC-ACN- AA-XB 826 EX-6

578.9 1.46 QC-ACN- AA-XB 827 EX-6

579.0 1.45 QC-ACN- AA-XB 828 EX-6

547.0 1.34 QC-ACN- TFA-XB 829 EX-6

561.0 1.27 QC-ACN- TFA-XB 830 EX-6

565.1 1.66 QC-ACN- AA-XB 831 EX-6

529.3 1.69 QC-ACN- AA-XB 832 EX-6

557.0 1.85 QC-ACN- AA-XB 833 EX-6

551.0 1.63 QC-ACN- AA-XB 834 EX-6

559.1 1.63 QC-ACN- AA-XB 835 EX-6

545.0 1.31 QC-ACN- TFA-XB 836 EX-6

569.1 1.3 QC-ACN- AA-XB 837 EX-6

559.1 1.31 QC-ACN- TFA-XB 838 EX-6

526.0 1.8 QC-ACN- AA-XB 839 EX-6

545.0 1.59 QC-ACN- AA-XB 840 EX-6

537.1 1.74 QC-ACN- AA-XB 841 EX-6

613.0 1.79 QC-ACN- AA-XB 842 EX-6

514.2 1.57 QC-ACN- AA-XB 843 EX-4

515.2 1.32 QC-ACN- TFA-XB 844 EX-4

485.4 1.74 QC-ACN- AA-XB 845 EX-4

563.3 1.56 QC-ACN- AA-XB 846 EX-4

515.1 1.32 QC-ACN- TFA-XB 847 EX-4

563.1 1.45 QC-ACN- AA-XB 848 EX-4

503.2 1.29 QC-ACN- TFA-XB 849 EX-4

527.2 1.67 QC-ACN- AA-XB 850  EX-100

545.0 1.3 QC-ACN- TFA-XB

TABLE 20 Fragment Ex. Starting LCMS R_(t) HPLC No. Material StructureMH⁺ (min) Method 851  EX-124

499 1.83 E 852  EX-124

515 1.75 E 853  EX-124

563.3 1.76 E 854 Ex-5

517.2 1.86 E 855 EX-5

602.4 1.89 E 856 EX-5

545.4 1.72 E 857 EX-5

519.3 1.49 E 858 EX-5

565.3 1.44 E 859 EX-5

489.3 1.46 E 860 EX-5

515.3 1.92 E 861 EX-5

545.3 1.9 E 862 EX-5

531.3 1.79 E 863 EX-5

517.3 1.21 E 864 EX-5

505.3 1.56 E 865 EX-5

523.3 1.18 F 866 EX-5

530.3 1.23 E 867 EX-5

503.3 1.26 E 868 EX-5

519.3 1.15 F 869 EX-5

545.4 1.69 E 870 EX-5

487.3 1.5 E 871 EX-5

531.3 1.16 F 872 EX-5

537.3 1.71 E 873 EX-5

529.4 1.77 E 874 EX-5

517.3 1.02 F 875 EX-5

519.3 1.51 E 876  EX-140

545.3 1.73 E 877  EX-140

531.3 1.73 E 878  EX-140

501.4 1.21 F 879  EX-140

503.4 1.29 F 880  EX-140

579.3 1.6 E 881  EX-140

531.3 1.56 E

Example 8821-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-morpholinopropan-1-one

To a two dram vial were added the TFA salt of6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine(0.025 g, 0.053 mmol), CH₃CN, HATU (1.0 equiv.), TEA (3.0 equiv.), and3-morpholinopropanoic acid (0.250 g, 1.570 mmol). The reaction vial wascapped and stirred overnight at room temperature. The mixture wasdiluted with solvent (90:10:0.1 CH₃CN:Water:TFA) and filtered. The crudematerial was purified via preparative LC/MS with the followingconditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile PhaseA: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B:95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 10-70% Bover 19 minutes, then a 3-minute hold at 100% B; Flow: 20 mL/min.Fractions containing the product were combined and dried via centrifugalevaporation to afford1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-3-morpholinopropan-1-one(21.2 mg, 0.041 mmol, 78% yield). LCMS MH⁺: 515.2 HPLC Ret. Time 1.52min. Method QC-ACN-AA-XB. ¹H NMR (500 MHz, DMSO-d₆) δ 8.85-8.72 (m, 1H),8.55-8.48 (m, 1H), 7.63-7.50 (m, 2H), 7.36-7.22 (m, 1H), 7.06-6.94 (m,1H), 4.63-4.51 (m, 1H), 4.06-3.98 (m, 1H), 3.63-3.56 (m, 5H), 3.30-3.20(m, 1H), 2.70-2.53 (m, 11H), 2.46-2.39 (m, 3H), 1.89-1.79 (m, 2H),1.70-1.59 (m, 1H), 1.53-1.46 (m, 1H), 1.45-1.39 (m, 6H).

The following examples were prepared according to the general processdescribed in Example 882.

TABLE 21 Template Ex. Starting LCMS R_(t) No. Material Structure MH⁺(min) HPLC Method 883 EX-2

529.0 1.63 QC-ACN-AA-XB 884 EX-2

563.2 1.29 QC-ACN-TFA-XB 885 EX-3

515.5 1.56 QC-ACN-AA-XB 886 EX-4

557.2 1.28 QC-ACN-TFA-XB 887 EX-4

543.2 1.44 QC-ACN-AA-XB 888 EX-4

531.2 1.32 QC-ACN-TFA-XB 889 EX-4

503.1 1.3 QC-ACN-AA-XB 890 EX-4

501.2 1.42 QC-ACN-AA-XB 891 EX-4

516.1 1.33 QC-ACN-AA-XB 892 EX-4

513.1 1.44 QC-ACN-AA-XB 893 EX-4

499.2 1.28 QC-ACN-TFA-XB 894 EX-4

501.2 1.31 QC-ACN-TFA-XB 895 EX-4

515.2 1.45 QC-ACN-AA-XB 896 EX-4

515.2 1.35 QC-ACN-TFA-XB 897 EX-4

558.2 1.42 QC-ACN-AA-XB 898 EX-4

531.2 1.35 QC-ACN-TFA-XB 899 EX-4

529.2 1.32 QC-ACN-AA-XB 900 EX-4

563.2 1.37 QC-ACN-TFA-XB 901 EX-4

517.2 1.32 QC-ACN-TFA-XB 902 EX-4

501.2 1.33 QC-ACN-TFA-XB 903 EX-4

487.1 1.29 QC-ACN-TFA-XB 904 EX-4

527.0 1.35 QC-ACN-TFA-XB 905 EX-4

473.1 1.31 QC-ACN-AA-XB 906 EX-4

557.2 1.65 QC-ACN-AA-XB 907 EX-4

626.2 1.56 QC-ACN-AA-XB 908 EX-4

555.2 1.62 QC-ACN-AA-XB 909 EX-4

543.2 1.32 QC-ACN-AA-XB 910 EX-4

541.2 1.5 QC-ACN-AA-XB 911 EX-4

557.2 1.48 QC-ACN-AA-XB 912 EX-4

570.2 1.31 QC-ACN-AA-XB 913 EX-4

542.2 1.44 QC-ACN-AA-XB 914 EX-4

517.2 1.32 QC-ACN-AA-XB 915 EX-4

557.2 1.43 QC-ACN-AA-XB 916 EX-4

513.1 1.38 QC-ACN-AA-XB 917 EX-4

543.2 1.35 QC-ACN-AA-XB 918 EX-4

513.2 1.39 QC-ACN-TFA-XB 919 EX-4

527.2 1.42 QC-ACN-TFA-XB 920 EX-4

541.2 1.49 QC-ACN-TFA-XB 921 EX-4

531.2 1.49 QC-ACN-AA-XB 922 EX-4

529.2 1.32 QC-ACN-AA-XB 923 EX-4

529.2 1.32 QC-ACN-AA-XB 924 EX-4

555.2 1.52 QC-ACN-TFA-XB 925 EX-4

505.2 1.31 QC-ACN-TFA-XB 926 EX-4

529.3 1.54 QC-ACN-TFA-XB

Example 927 Azetidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate

1-(tert-butoxycarbonyl)azetidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate(15 mg, 0.026 mmol) and 2:1 trifluoroacetic acid:dichloromethane (1.2mL, 0.026 mmol) were combined in a 1-dram vial containing a stir bar.The resulting clear, yellow solution was stirred at room temperature for30 min. After completion of the reaction, toluene (150 μL) was added tothe reaction mixture. The reaction mixture was stirred briefly andexcess solvent was evaporated. The residue was taken up in DMF (1.5 mL)and purified by semi-preparative HPLC on a C-18 column on the Shimadzuinstrument, eluting with water/acetonitrile/TFA. Excess solvent wasevaporated from product-containing fractions to afford azetidin-3-yl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate,TFA (14.9 mg, 0.025 mmol, 96% yield) as a white solid. LCMS MH⁺: 487.3.HPLC Ret. Time 1.40 min. Method QC-ACN-TFA-XB. ¹H NMR (400 MHz,METHANOL-d₄) δ 8.68 (s, 1H), 8.58 (s, 1H), 7.60 (s, 1H), 7.33 (d, J=8.3Hz, 1H), 7.08 (dd, J=8.4, 1.5 Hz, 1H), 5.33-5.24 (m, 1H), 4.45 (dd,J=12.7, 7.0 Hz, 2H), 4.38-4.25 (m, 2H), 4.21 (br. s., 2H), 3.17-3.06 (m,1H), 2.98 (dq, J=13.6, 6.8 Hz, 4H), 2.88 (tt, J=12.0, 3.3 Hz, 1H), 2.67(s, 3H), 2.30 (s, 3H), 1.96 (d, J=12.0 Hz, 2H), 1.75 (br. s., 2H), 1.40(d, J=7.1 Hz, 6H).

The following examples were prepared according to the general processdescribed in Example 929.

TABLE 22 Ex. LCMS R_(t) HPLC No. Structure MH⁺ (min) Method 928

475.1 1.45 QC-ACN-TFA-XB 929

501.4 1.48 QC-ACN-TFA-XB 930

515.4 1.42 QC-ACN-TFA-XB 931

501.4 1.37 QC-ACN-TFA-XB 932

529.3 1.54 QC-ACN-AA-XB 933

515.4 1.4 QC-ACN-TFA-XB 934

489.4 1.36 QC-ACN-TFA-XB 935

515.4 1.4 QC-ACN-TFA-XB 936

529.4 1.52 QC-ACN-AA-XB 937

515.0 1.52 QC-ACN-TFA-XB 938

515.0 1.58 QC-ACN-AA-XB 939

515.1 1.52 QC-ACN-TFA-XB 940

501.1 1.55 QC-ACN-AA-XB 941

501.4 1.37 QC-ACN-TFA-XB 942

528.9 1.64 QC-ACN-AA-XB 943

503.4 1.35 QC-ACN-TFA-XB 944

526.3 1.37 QC-ACN-TFA-XB 945

543.5 1.45 QC-ACN-TFA-XB 946

593.4 1.45 QC-ACN-TFA-XB 947

543.5 1.45 QC-ACN-TFA-XB 948

529.5 1.41 QC-ACN-TFA-XB 949

531.3 1.47 QC-ACN-TFA-XB 950

573.1 1.55 QC-ACN-AA-XB 951

558.1 1.48 QC-ACN-AA-XB 952

545.0 1.8 QC-ACN-AA-XB 953

265.2 1.52 QC-ACN-TFA-XB 954

515.1 1.67 QC-ACN-AA-XB 955

545.1 1.76 QC-ACN-AA-XB 956

529.1 1.59 QC-ACN-TFA-XB

Example 957(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-methylpiperazin-1-yl)methanone

6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (10 mg, 0.026 mmol) was dissolved in THF (0.25 mL). Phenylcarbonochloridate (6.06 mg, 0.039 mmol) was added to the solution. Thereaction mixture was stirred overnight at room temperature. The reactionmixture was blown down on a ZYmark Turbovap at 45° C. for 1 h. Theresidue was dissolved in NMP (0.25 mL). Next, 1-methylpiperazine (7.75mg, 0.077 mmol) and DIPEA (6.76 μl, 0.039 mmol) were added to the NMPsolution of the intermediate. The reaction mixture was stirred at 100°C. overnight. Crude samples with final volume of 1.8 mL in DMF/NMP in astubby tube were purified via preparative LC/MS with the followingconditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile PhaseA: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B:95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 20-60% Bover 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min.Fractions containing the product were combined and dried via centrifugalevaporation to afford(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-methylpiperazin-1-yl)methanone (4 mg, 7.63 μmol, 29.6% yield). LCMS MH⁺: 514.4. HPLC Ret.Time 1.29 min. Method QC-ACN-TFA-XB.

The following examples were prepared according to the general processdescribed in Example 957.

TABLE 23 Ex. Starting LCMS R_(t) No. Material Structure MH⁺ (min) HPLCMethod 958 EX-4

565.9 1.57 QC-ACN-AA-XB 959 EX-4

488.3 1.27 QC-ACN-TFA-XB 960 EX-4

540.5 1.46 QC-ACN-TFA-XB 961 EX-4

500.0 1.31 QC-ACN-AA-XB 962 EX-4

474.4 1.27 QC-ACN-AA-XB 963 EX-4

528.5 1.56 QC-ACN-AA-XB 964 EX-4

514.2 1.36 QC-ACN-AA-XB 965 EX-4

542.6 1.83 QC-ACN-AA-XB 966 EX-4

528.5 1.39 QC-ACN-TFA-XB 967 EX-4

486.0 1.55 QC-ACN-AA-XB 968 EX-4

500.5 1.31 QC-ACN-AA-XB 969 EX-4

577.6 1.45 QC-ACN-TFA-XB 970 EX-4

528.5 1.33 QC-ACN-TFA-XB 971 EX-4

500.3 1.3 QC-ACN-TFA-XB 972 EX-4

488.0 1.43 QC-ACN-TFA-XB 973 EX-4

542.0 1.68 QC-ACN-AA-XB 974 EX-4

528.4 1.32 QC-ACN-TFA-XB 975 EX-4

572.5 1.45 QC-ACN-TFA-XB 976 EX-4

557.3 1.3 QC-ACN-AA-XB 977 EX-4

528.4 1.36 QC-ACN-TFA-XB 978 EX-4

502.4 1.33 QC-ACN-AA-XB 979 EX-4

544.5 1.3 QC-ACN-TFA-XB 980 EX-4

542.6 1.41 QC-ACN-TFA-XB

Example 9812-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)acetonitrile

Intermediate 981A: 3-isopropyl-1H-indole

To a 500 mL round bottom flask were added 2,2,2-trichloroacetic acid(23.60 g, 144 mmol), toluene (150 mL), and triethylsilane (46.1 mL, 289mmol). With stirring, the solution was heated to 70° C. and a solutionof 1H-indole (11.28 g, 96 mmol) and acetone (8.48 mL, 116 mmol) in 75 mLof toluene was added drop-wise via an addition funnel. The reactionmixture was heated to 90° C. for 2.5 hours. The reaction mixture wascooled to room temperature, then to 5° C. To this were added 1.5 Mdibasic potassium phosphate solution and diethyl ether. The layers wereseparated and the organic layer was washed with brine, dried overNa₂SO₄, filtered and concentrated. The residue was purified on silicagel using ethyl acetate/hexane as the eluent to afford3-isopropyl-1H-indole (12 g, 78%) as a white solid. LC retentiontime=1.04 min [A1]. MS (E⁺) m/z: 160.2 (M+H). ¹H NMR (400 MHz,CHLOROFORM-d) δ 7.72-7.65 (m, 1H), 7.41-7.36 (m, 1H), 7.21 (d, J=0.9 Hz,1H), 7.14 (s, 1H), 6.99 (dd, J=2.2, 0.7 Hz, 1H), 3.31-3.17 (m, 1H), 1.40(d, J=6.8 Hz, 6H).

Intermediate 981B:6-(3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine

To a 100 mL round bottom flask were added 3-isopropyl-1H-indole (1.000g, 6.28 mmol) and DCE (10 mL). NBS (1.062 g, 5.97 mmol) was dissolved in10 mL of DCE and added to the reaction mixture drop-wise via an additionfunnel over 15 minutes. The reaction was quenched with 5 mL of a 10%sodium sulfite solution. The volatiles were removed. Next, THF (10 mL),7,8-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(1.54 g, 5.56 mmol), PdCl₂(dppf)-CH₂Cl₂ adduct (0.25 g, 0.314 μmol), and3 M tribasic potassium phosphate solution (6.3 mL, 18.8 mmol) wereadded. The reaction vessel was capped and pump/purged with nitrogen gasthree times. The reaction mixture was set to heat at 70° C. for 1 hour.The mixture was cooled to room temperature and concentrated. The cruderesidue was taken up in DCM (3 mL), filtered and purified on silica gelusing ethyl acetate/hexane to afford6-(3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(0.8 g, 41.8%) as a white foam. LC retention time=2.04 min [D1]. MS (E⁺)m/z: 305.0 (M+H). ¹H NMR (400 MHz, METHANOL-d₄) δ 8.54-8.44 (m, 1H),8.38-8.28 (m, 1H), 7.56 (d, J=1.1 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H),7.13-7.01 (m, 2H), 3.28-3.16 (m, 1H), 2.66 (s, 3H), 2.32 (s, 3H), 1.38(d, J=6.8 Hz, 6H).

Intermediate 981C: tert-butyl5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate

To a 40 mL reaction vial were added6-(3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(0.450 g, 1.478 mmol), AcOH (4 mL), water (0.5 mL), and NBS (0.263 g,1.478 mmol). The vial was sealed and stirred at 80° C. for 30 minutes.The reaction mixture was cooled to room temperature and 1 mL of a 10%sodium sulfite was added. This mixture was concentrated, dissolved inDCM/MeOH, filtered, and purified on silica gel using ethylacetate/hexane to afford5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indoleas a tan solid. LC retention time=1.01 min [A1]. MS (E⁺) m/z: 83/385(M+H). ¹H NMR (400 MHz, DMSO-d₆) δ 11.26 (s, 1H), 8.82 (s, 1H), 8.48 (s,1H), 7.70 (d, J=8.4 Hz, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.16 (dd, J=8.6,1.8 Hz, 1H), 2.88 (br d, J=14.1 Hz, 1H), 2.60 (s, 3H), 2.15 (s, 3H),1.43-1.15 (m, 5H), 1.18-1.09 (m, 1H).

To this material were added DMAP (0.010 g, 0.0148 mmol), THF (10 mL),and BOC-anhydride (0.59 g, 2.95 mmol). The reaction mixture was stirredfor 2 hours at room temperature, concentrated to a viscous oil, dilutedwith DCM, and washed with dilute 1N HCl. The organic was washed withwater and then brine. The solution was dried over Na₂SO₄, filtered, andconcentrated. The residue was purified on silica gel using ethylacetate/hexane to afford tert-butyl5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate(0.45 g, 63%) as a yellowish solid. LC retention time=1.15 min [A1]. MS(E⁺) m/z: 483/485 (M+H).

Intermediate 981D: tert-butyl5-(8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate

To a mixture of tert-butyl5-bromo-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate(0.130 g, 0.269 mmol), PdCl₂(dppf)-CH₂Cl₂ adduct (10.98 mg, 0.013 mmol),and (8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3-en-3-yl) boronicacid (0.071 g, 0.282 mmol) in a screw cap vial was added THF (2 mL)followed by 3 M aqueous solution of tripotassium phosphate (0.269 mL,0.807 mmol). The vial was fitted with a Teflon lined septum cap. Thesystem was evacuated under vacuum and backfilled with nitrogen gas. Theprocedure was repeated three times. The vial was sealed and heated at75° C. for 18 hours. The reaction mixture was diluted with EtOAc (100mL) and poured into a separatory funnel. The organic layer was washedwith water (2×50 mL), saturated aqueous NaCl solution (50 mL), dried(Na₂SO₄), filtered and concentrated in vacuo to afford crude product.The crude product was purified on silica gel using 0-100% ethylacetate/hexane. Following concentration of the fractions, the productwas collected as a tan oil (0.11 g, 65%). LC retention time=1.19 min[A1]. MS (E⁺) m/z: 612.2 (M+H).

Intermediate 981E: tert-butyl5-(8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate

In a Parr bottle, tert-butyl5-(8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]oct-2-en-3-yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate(0.11 g, 0.18 mmol) was suspended in ethyl acetate (3 mL) and treatedwith 10 mol % of 5% Pd/C (0.057 g, 0.027 mmol). Following degassing, thereaction mixture was placed under a hydrogen gas atmosphere (50 psi) andshaken for 16 hours at room temperature. Following the removal of thehydrogen atmosphere and back-filling with nitrogen gas, the reactionmixture was diluted with MeOH, filtered through celite, and concentratedto afford tert-butyl5-(8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate (0.11 g, 100%)as a mixture of isomers. LC retention time=1.20 min [A1]. MS (E⁺) m/z:614.4 (M+H).

Intermediate 981F:6-(5-(8-azabicyclo[3.2.1]octan-3-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridineTFA salt

To a solution of tert-butyl5-(8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indole-1-carboxylate(0.025 g, 0.041 mmol) was added DCM (0.5 mL) in a 2 dram reaction vial.To this was added TFA (1 mL) and the reaction vial was capped. Thereaction mixture was stirred for 2 hours at room temperature. Thevolatiles were removed under a stream of nitrogen gas. The yield wasconsidered quantitative. This material was used as is for finalderivatization to prepare the compounds shown in Table 24. One exampleis described below for Example 981.

Example 981

In a 2 dram reaction vial were added6-(5-(8-azabicyclo[3.2.1]octan-3-yl)-3-isopropyl-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine,TFA salt (0.021 g, 0.041 mmol), NMP, DBU (0.025 mL, 0.164 mmol), anddrop-wise, bromoacetonitrile (0.017 g, 0.15 mmol). The reaction mixturewas stirred for 1 hour at room temperature, then diluted with water, andfiltered through a 0.45 micron syringe filter. The crude material waspurified via preparative LC/MS with the following conditions: Column:XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5acetonitrile:water with 10-mM ammonium acetate; Gradient: 40-80% B over25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractionscontaining the product were combined and dried via centrifugalevaporation. The material was further purified via preparative LC/MSwith the following conditions: Column: XBridge C18, 19×200 mm, 5-μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammoniumacetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammoniumacetate; Gradient: 35-75% B over 20 minutes, then a 5-minute hold at100% B; Flow: 20 mL/min. Fractions containing the product were combinedand dried via centrifugal evaporation.2-(3-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)acetonitrile(0.0021 g, 6.4% yield) was collected as a mixture of isomers. Twoanalytical LC/MS injections were used to determine the final purity. LCretention time 2.18 min [C1]. MS (E⁺) m/z: 453.0 (M+H). ¹H NMR (500 MHz,DMSO-d₆) δ 10.95 (br d, J=18.2 Hz, 1H), 8.73-8.64 (m, 1H), 8.69 (br s,1H), 8.52-8.39 (m, 1H), 8.46 (s, 1H), 7.62 (s, 1H), 7.62 (br d, J=18.2Hz, 1H), 7.19 (s, 1H), 7.23 (br s, 1H), 7.01-6.88 (m, 1H), 7.05-6.84 (m,1H), 3.34 (br s, 1H), 3.17 (s, 1H), 3.13-3.01 (m, 1H), 2.99-2.93 (m,1H), 2.88-2.76 (m, 1H), 2.57 (s, 2H), 2.15 (s, 2H), 2.02-1.94 (m, 1H),1.90 (br d, J=8.2 Hz, 1H), 1.75 (br s, 4H), 1.68-1.57 (m, 1H), 1.29 (brs, 5H).

The following examples were prepared according to the general proceduresdisclosed in Example 981.

TABLE 24 Ex. LCMS R_(t) HPLC No. Structure MH⁺ (min) Method 982

499.1 1.57 C1 983

499.1 1.50 C1 984

520.0 1.58 C1 985

520.1 1.53 C1

Example 9866-(3-isopropyl-5-(1-(pyridin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine

6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (19.4 mg, 0.050 mmol), 2-chloropyridine (6.2 mg, 0.055 mmol),4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (5.8 mg, 10.00 μmol),Pd₂(dba)₃ (4.6 mg, 5.00 μmol) and Cs₂CO₃ (48.9 mg, 0.150 mmol) weresuspended in dioxane (0.5 mL). The mixture was degassed with nitrogengas for 5 minutes. The reaction vessel was sealed and heated to 90° C.for 2 hours. Upon completion, the reaction mixture was filtered,concentrated, dissolved in DMF, and purified via preparative LCMS usingthe following conditions: Column: XBridge C18, 19×200 mm, 5-μmparticles; Mobile Phase A: 5:95 acetonitrile:water with 0.1%trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1%trifluoroacetic acid; Gradient: 10-50% B over 19 minutes, then a5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing theproduct were combined and dried via centrifugal evaporation to afford6-(3-isopropyl-5-(1-(pyridin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine,TFA (10.1 mg, 0.017 mmol, 35% yield). LCMS retention time 1.25[QC-ACN-TFA-XB]. MS (ES⁺) m/z: 465.4 (M+H). ¹H NMR (500 MHz, DMSO-d₆) δ8.81 (s, 1H), 8.63 (br d, J=7.9 Hz, 1H), 8.44-8.38 (m, 2H), 8.36 (br d,J=9.5 Hz, 1H), 7.82-7.73 (m, 1H), 7.67 (s, 1H), 7.48 (d, J=8.5 Hz, 1H),7.28-7.24 (m, 1H), 7.22 (d, J=7.9 Hz, 1H), 7.12 (br d, J=8.5 Hz, 1H),3.41 (br d, J=11.3 Hz, 2H), 3.11-2.93 (m, 3H), 2.85 (dt, J=14.0, 7.0 Hz,1H), 2.42 (s, 3H), 2.06-1.96 (m, 2H), 1.96-1.82 (m, 5H), 1.35 (dd,J=16.5, 7.0 Hz, 6H).

The following examples were prepared in a manner similar to Example 986.

TABLE 25 Ex. LCMS R_(t) No. Structure MH⁺ (min) HPLC Method 987

522.5 0.96 QC-ACN-TFA-XB 988

522.5 0.95 QC-ACN-TFA-XB

Example 9896-(3-isopropyl-5-(1-(pyrimidin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo)[1,5-a]pyridine

6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (19.4 mg, 0.050 mmol) and Et₃N (0.021 mL, 0.150 mmol) weremixed in DMSO (1 mL). Next, 2-chloropyrimidine (6.9 mg, 0.060 mmol) wasadded. The reaction vial was sealed and heated to 90° C. for 2 hours.Upon completion, the reaction mixture was cooled to room temperature,diluted with water (0.05 mL) and 1 mL of DMSO, and purified onpreparative LCMS via the following conditions: Column: XBridge C18,19×200 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with10-mM ammonium acetate; Gradient: 45-100% B over 20 minutes, then a10-minute hold at 100% B; Flow: 20 mL/min. Fractions containing theproduct were combined and dried via centrifugal evaporation to provide6-(3-isopropyl-5-(1-(pyrimidin-2-yl)piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(5.0 mg, 10.2 μmol, 20.4% yield). LCMS retention time 1.71[QC-ACN-TFA-XB]. MS (ES⁺) m/z: 466.3 (M+H).

Example 9902-(4-(2-(8-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide

To a solution of2-(4-(2-(8-(benzylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (0.040 g, 0.073 mmol) in methanol(10.0 mL) was added Pd/C (0.023 g, 0.218 mmol). The reaction mixture wasstirred at room temperature for 6 h under hydrogen. The reaction mixturewas diluted with ethyl acetate:methanol (1:1) filtered and washed withexcess ethyl acetate. The combined organic layers were evaporated toafford crude compound. The crude material was purified via preparativeLC/MS with the following conditions: Column: Waters XBridge C18, 19×150mm, 5-μm particles; Mobile Phase A: 0.05% TFA; Mobile Phase B:acetonitrile; Gradient: 15-50% B over 20 minutes, then a 5-minute holdat 100% B; Flow: 15 mL/min. Fractions containing the product werecombined and dried via centrifugal evaporation to afford2-(4-(2-(8-amino-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (7.3 mg). LCMS retention time 1.44min [E]. MS (E−) m/z: 460.3 (M−H). ¹H NMR (400 MHz, METHANOL-d₄) δ ppm8.31-8.39 (m, 1H) 8.16 (d, J=1.47 Hz, 1H) 7.66 (s, 1H) 7.36 (d, J=8.31Hz, 1H) 7.08 (d, J=8.80 Hz, 1H) 6.84-6.97 (m, 1H) 4.26 (s, 2H) 3.76 (d,J=13.21 Hz, 2H) 3.33-3.43 (m, 2H) 3.25 (br. s., 2H) 2.94-3.12 (m, 8H)2.19 (br. s., 4H) 1.50 (d, J=7.09 Hz, 7H) 1.28 (br. s., 1H).

Example 9912-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide

Intermediate 991A: 4-fluoro-3-isopropyl-1H-indole

To a 40 mL vial with a red pressure-release cap were added2,2,2-trichloroacetic acid (0.907 g, 5.55 mmol), toluene (7.40 mL) andtriethylsilane (1.773 mL, 11.10 mmol). With stirring, the solution washeated to 70° C. and a solution of 4-fluoro-1H-indole (0.500 g, 3.70mmol) and acetone (0.326 mL, 4.44 mmol) in 1 mL of toluene was addeddrop-wise via a syringe. The reaction mixture was stirred and heated to90° C. for 3 h, venting with a nitrogen line. The reaction mixture wasallowed to cool to 5° C., and to the reaction mixture were added 1 Maqueous K₃PO₄ solution (˜4 mL) and ethyl acetate (4 mL). The layers wereseparated and the aqueous phase was extracted with EtOAc (2×5 mL). Thecombined organic extracts were dried over sodium sulfate and filtered,and excess solvent was evaporated off. The resulting red oil was takenup in DCM (˜2 mL) and purified by flash chromatography to afford4-fluoro-3-isopropyl-1H-indole as a yellow liquid (483.2 mg, 2.67 mmol,72.2% yield). ¹H NMR (400 MHz, CHLOROFORM-d) δ 7.97 (br s, 1H),7.16-7.07 (m, 2H), 6.95 (d, J=2.2 Hz, 1H), 6.77 (ddd, J=11.3, 7.4, 1.1Hz, 1H), 3.38 (dt, J=13.7, 6.8 Hz, 1H), 1.38 (dd, J=6.8, 0.6 Hz, 6H).HPLC Ret. Time 0.99 min. Method G.

Intermediate 991B: 4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole

4-fluoro-3-isopropyl-1H-indole (0.475 g, 2.68 mmol) was dissolved in THF(10.72 mL) in a 40 mL vial. The solution was cooled to 0° C. under anitrogen atmosphere with an ice bath, and sodium hydride (0.214 g, 5.36mmol) was added to the reaction mixture. The reaction mixture wasallowed to warm to room temperature, then triisopropylsilyl chloride(0.860 mL, 4.02 mmol) was added dropwise via syringe. The reactionmixture was then stirred at 50° C. for 1 h. The reaction completed. Thereaction mixture was cooled to 0° C. and quenched by addition of 1 MKHSO₄ (˜4 mL) and water (4 mL). Ethyl acetate (4 mL) was added, and thephases were separated. The aqueous phase was extracted with ethylacetate (2×3 mL). The combined organic phases were extracted with brine(1×4 mL), and excess solvent was evaporated off. The resulting yellowoil was taken up in DCM (˜3.5 mL total volume) and purified by flashchromatography on a 24 g silica column, eluting with ethyl acetate andhexanes. The product4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole was obtained as aclear, colorless liquid (0.92 g, 2.48 mmol, 92% yield). ¹H NMR (400 MHz,CHLOROFORM-d) δ 7.24 (d, J=8.3 Hz, 1H), 7.03 (td, J=8.1, 5.4 Hz, 1H),6.94 (s, 1H), 6.76 (dd, J=11.0, 7.8 Hz, 1H), 3.36 (spt, J=6.8 Hz, 1H),1.36 (d, J=6.8 Hz, 6H), 1.16 (d, J=7.6 Hz, 18H). LCMS MH⁺: 334.3. HPLCRet. Time 1.43 min. Method G.

Intermediate 991C:5-bromo-4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole

Sec-butyllithium (2.144 mL, 3.00 mmol, 90% purity) was added to a −75°C. (dry ice/methanol bath) solution of4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole (0.910 g, 2.73mmol) and 1,1,4,7,7-pentamethyldiethylenetriamine (0.572 mL, 2.73 mmol)in THF (13.64 mL) in an oven-dried 50 mL recovery flask under a nitrogenatmosphere. The solution was stirred for 6.5 h at −75° C. for 6 h. Next,1,2-dibromotetrafluoroethane (0.325 mL, 2.73 mmol) was added to thereaction mixture. The solution was stirred for 10 min at −75° C., thenallowed to warm to room temperature. The reaction progressed 50%. Excesssolvent was evaporated from the reaction mixture. The resulting orangeoil was taken up in DCM (total volume ˜4 mL) and purified by flashchromatography on a 24 g silica column, eluting with hexanes. Theproduct and remaining starting indole co-eluted. Fractions were pooledand excess solvent was evaporated off to yield5-bromo-4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole (1.07 g,1.68 mmol, 65% yield) and4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole as a mixture in aclear, colorless liquid. The mixed products were taken forward directly.LCMS MH⁺: 412.08.

HPLC Ret. Time 1.50 min. Method G.

Intermediate 991D: tert-butyl4-(4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate

5-bromo-4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indole (650 mg,1.576 mmol) was dissolved in THF (7880 μl) in a 40 mL scintillation vialwith a red pressure-release cap and containing a Teflon-covered stirbar. Tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate(585 mg, 1.891 mmol) was added to the vial, followed by tripotassiumphosphate (2364 μl, 4.73 mmol). The reaction mixture was degassed bybubbling nitrogen through the solution for 5 min, then 2nd generationXPhos precatalyst (31.0 mg, 0.039 mmol) was added to the reactionmixture. The clear, yellow reaction mixture was placed under a nitrogenatmosphere and heated to 60° C. with stirring for 6 h. The reactionmixture was allowed to cool to room temperature. The aqueous phase wasremoved, and excess THF was evaporated from the reaction. The resultingoil residue was taken up in DCM (˜4 mL total volume) and purified byflash chromatography eluting with ethyl acetate and hexanes. The productfractions was concentrated and vacuumed to afford tert-butyl4-(4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylateas a pale yellow sticky solid (0.65 g, 1.14 mmol, 72.6% yield). ¹H NMR(400 MHz, CHLOROFORM-d) δ 7.18 (d, J=8.6 Hz, 1H), 6.99-6.94 (m, 1H),6.92 (s, 1H), 5.90 (br s, 1H), 4.10 (br s, 2H), 3.66 (br t, J=5.2 Hz,2H), 3.36 (spt, J=6.8 Hz, 1H), 2.61 (br s, 2H), 1.53 (s, 9H), 1.35 (d,J=6.7 Hz, 6H), 1.16 (d, J=7.6 Hz, 18H). LCMS MH⁺: 515.5. HPLC Ret. Time1.53 min. Method G.

Intermediate 991E: tert-butyl4-(4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indol-5-yl)piperidine-1-carboxylate

5% Pd on Carbon (100 mg, 1.271 mmol) was weighed into a 20 mLscintillation vial containing a Teflon-coated stir bar with a redpressure-release cap. Tert-butyl4-(4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate(654.4 mg, 1.271 mmol) was dissolved in MeOH (12.71 mL) and transferredinto the vial containing the Pd on C while under a nitrogen atmosphere.Ammonium formate (401 mg, 6.36 mmol) was added to the reaction mixture,and the vial was capped. The reaction mixture was stirred at 50° C. for4 h. Additional ammonium formate (401 mg, 6.36 mmol) was added to thereaction mixture, and the reaction mixture was stirred at 60° C. for 3 hbut did not reach completion. The reaction mixture was stirred at 50° C.overnight. The reaction mixture was filtered through celite to removePd/C. Excess methanol was evaporated from the reaction mixture to affordtert-butyl 4-(4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indol-5-yl)piperidine-1-carboxylate (654 mg, 1.271 mmol, 100% yield, 30% purity) aclear, pale yellow oil. Product was checked by ¹H NMR and wasapproximately 30% reduced and 70% starting material alkene. LCMS MH⁺:517.5. HPLC Ret. Time 1.53 min. Method G.

Intermediate 991F:tert-butyl-4-(4-fluoro-3-isopropyl-1H-indol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Tert-butyl4-(4-fluoro-3-isopropyl-1-(triisopropylsilyl)-1H-indol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate(0.650 g, 1.263 mmol) (7:3 mix of piperidine alkene and piperidinealkane) and tetra-n-butylammonium fluoride (0.660 g, 2.53 mmol) weredissolved in THF (6.31 mL) in a 20 mL scintillation vial. The reactionmixture was stirred for 10 min at room temperature. The reaction wascomplete with 2 peaks corresponding to the product alkene (1.15 min,M+H⁺=359.3) and alkane (1.16 min, M+H⁺=359.3, 361.3). The reactionmixture was partitioned between brine and ethyl acetate (1:1, totalvolume ˜16 mL). The phases were separated, and the aqueous phase wasextracted with ethyl acetate (2×4 mL). The combined organic phases werewashed with brine (2×5 mL), dried over sodium sulfate, and filtered.Excess solvent was evaporated from the organic phase to affordtert-butyl4-(4-fluoro-3-isopropyl-1H-indol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate(0.476 g, 1.263 mmol) as a pale yellow oil. LCMS MH⁺: 359.3. HPLC Ret.Time 1.15 min. Method G.

Intermediate 991G: tert-butyl4-(4-fluoro-3-isopropyl-1H-indol-5-yl)-3,6-dihydropyridine-1(2H)-carboxylate

5% Pd on Carbon (150 mg, 1.264 mmol) was weighed into a 20 mLscintillation vial containing a Teflon-coated stir bar with a redpressure-release cap. Tert-butyl4-(4-fluoro-3-isopropyl-1H-indol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate(453 mg, 1.264 mmol) was dissolved in MeOH (6.32 mL) and transferredinto the vial containing the Pd on C while under a nitrogen atmosphere.Ammonium formate (797 mg, 12.64 mmol) was added to the reaction mixture,and the vial was capped. The reaction mixture was stirred at 60° C. for30 min. The reaction completed. The reaction mixture was filteredthrough celite to remove Pd/C. Excess methanol was evaporated from thereaction mixture. The resulting yellow oil was taken up in DCM (3 mL)and purified by flash chromatography on a 24 g silica column, elutingwith ethyl acetate and hexanes to afford tert-butyl4-(4-fluoro-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate as awhite crystalline solid (370.3 mg, 1.017 mmol, 80% yield). ¹H NMR (400MHz, CHLOROFORM-d) δ 7.96 (br s, 1H), 7.10 (d, J=8.4 Hz, 1H), 7.02-6.97(m, 1H), 6.93 (d, J=2.1 Hz, 1H), 4.28 (br s, 2H), 3.37 (spt, J=6.8 Hz,1H), 3.17 (tt, J=12.0, 3.6 Hz, 1H), 2.88 (br t, J=11.3 Hz, 2H),1.89-1.81 (m, 2H), 1.81-1.68 (m, 2H), 1.52 (s, 9H), 1.36 (d, J=6.8 Hz,6H). LCMS MH⁺: 361.3. HPLC Ret. Time 1.16 min. Method G.

Intermediate 991H: tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-indole-1-carboxylate

Tert-butyl4-(4-fluoro-3-isopropyl-1H-indol-5-yl)piperidine-1-carboxylate (370 mg,1.026 mmol) and di-tert-butyl dicarbonate (540 μl, 2.258 mmol) weredissolved in THF (5132 μl) in a 20 mL vial containing a Teflon-coveredstir bar. Next, 4-dimethylaminopyridine (12.54 mg, 0.103 mmol) wasadded. The vial was capped and the clear, pale yellow solution wasstirred at room temperature for 2 h. The reaction finished. Excesssolvent was evaporated from the reaction mixture. The residue was takenup in DCM (˜2 mL) and purified by flash chromatography on a 24 g silicacolumn, eluting with ethyl acetate and hexanes to afford tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-indole-1-carboxylateas a white foam (4.57 g, 0.98 mmol, 99% yield). ¹H NMR (400 MHz,CHLOROFORM-d) δ 7.85 (br s, 1H), 7.28 (br s, 1H), 7.12 (dd, J=8.4, 7.2Hz, 1H), 3.29 (spt, J=6.8 Hz, 1H), 3.14 (tt, J=12.0, 3.5 Hz, 1H), 2.87(br t, J=11.4 Hz, 2H), 1.88-1.79 (m, 2H), 1.51 (s, 9H), 1.34 (d, J=6.8Hz, 6H). LCMS MH⁺: 461.4. HPLC Ret. Time 1.36 min. Method G.

Intermediate 9911: tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate

Tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-indole-1-carboxylate(456.7 mg, 0.992 mmol) and2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (324 μl, 1.587mmol) were dissolved in THF (7933 μl) in a 20 mL vial containing aTeflon-covered stir bar. The vial was cooled to −20° C. (dry ice/NMPbath) under a nitrogen atmosphere. Lithium diisopropylamide (992 μl,1.983 mmol) was added dropwise to the vial (via a syringe through theseptum cap) over ˜5 min. The reaction mixture was stirred at −20° C. for1 h, then allowed to slowly warm to 0° C. Most starting material (˜75%)converted to product. The reaction mixture was allowed to warm to 10°C., then quenched by addition of 1 M KHSO₄ (5 mL). The resulting mixturewas extracted with EtOAc (2×3 mL). The combined organic extracts werewashed with brine (2×3 mL), and excess solvent was evaporated off. Theresidue was taken up in DCM (2 mL) and purified by flash chromatographyon a 24 g silica column, eluting with ethyl acetate and hexane to affordtert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylateas a white solid (468.9 mg, 0.72 mmol, 72.6% yield, 90% purity). ¹H NMR(400 MHz, CHLOROFORM-d) δ 7.61 (d, J=8.6 Hz, 1H), 7.06 (dd, J=8.4, 7.1Hz, 1H), 4.28 (br s, 2H), 3.35-3.26 (m, 1H), 3.14 (br s, 1H), 2.87 (brt, J=11.9 Hz, 2H), 1.88-1.81 (m, 2H), 1.71 (br s, 2H), 1.67 (s, 9H),1.44 (s, 12H). LCMS MH⁺-56: 531.4. HPLC Ret. Time 1.39 min. Method G.

Intermediate 991J: tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-(8-ethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-indole-1-carboxylate

Tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate(100 mg, 0.170 mmol) and6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (42.8 mg, 0.188 mmol)were weighed into a 1-dram vial with a red pressure-release cap andcontaining a Teflon-coated stir bar. THF (852 μl) and tripotassiumphosphate (170 μl, 0.511 mmol) were added to the vial, and the reactionmixture was degassed by bubbling nitrogen through the reaction mixturefor 3 min. 2ND generation XPhos precatalyst (4.02 mg, 5.11 μmol) wasadded to the vial, and the reaction mixture was placed under a nitrogenatmosphere and stirred at 60° C. overnight. The reaction was completed.The aqueous phase was removed, and excess solvent was evaporated fromthe organic phase. The resulting orange residue was taken up in DCM (˜3mL) and purified by flash chromatography on a 12 g silica column,eluting with ethyl acetate and hexanes to afford tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indole-1-carboxylateas a cloudy colorless glass (100.7 mg, 0.124 mmol, 72.9% yield, 75%purity). ¹H NMR (400 MHz, CHLOROFORM-d) δ 8.36 (s, 1H), 8.22 (d, J=1.1Hz, 1H), 8.04 (d, J=8.7 Hz, 1H), 7.28 (s, 1H), 7.23 (dd, J=8.6, 7.2 Hz,1H), 6.72 (d, J=1.0 Hz, 1H), 4.39-4.22 (m, 2H), 4.04 (s, 3H), 3.19 (tt,J=12.0, 3.3 Hz, 1H), 2.99 (dtd, J=14.1, 7.0, 3.0 Hz, 1H), 2.88 (br t,J=11.2 Hz, 2H), 1.91-1.82 (m, 2H), 1.74 (br dd, J=12.5, 3.8 Hz, 2H),1.50 (s, 9H), 1.24 (d, J=2.0 Hz, 15H). LCMS MH⁺: 608.6. HPLC Ret. Time1.22 min. Method G.

Example 991

Tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indole-1-carboxylate(25 mg, 0.041 mmol) was Boc-deprotected by reacting with 2:1trifluoroacetic acid/dichloromethane (1.2 mL, 0.041 mmol) in a 1-dramvial for 30 min. Toluene (˜0.15 mL) was added, and excess solvent wasthen evaporated from the reaction mixture. The resulting residue wasstirred with 2-chloro-N,N-dimethylacetamide (10.00 mg, 0.082 mmol) andpotassium carbonate (28.4 mg, 0.206 mmol) in NMP (0.411 mL) at 22° C.for 1.5 h. The reaction did not finish. The reaction mixture was stirredat 22° C. over the weekend. The reaction was completed. The reactionmixture was partitioned between water and ethyl acetate (3 mL totalvolume), and the aqueous phase was extracted with ethyl acetate (2×1mL). Excess solvent was evaporated from the combined organic extracts.DMF (˜1.5 mL) was added to the resulting residue. The crude material waspurified via preparative LC/MS with the following conditions: Column:XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-55% B over20 minutes, then a 4-minute hold at 100% B; Flow: 20 mL/min. Fractionscontaining the product were combined and dried via centrifugalevaporation to afford2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide(8.5 mg, 0.017 mmol, 42.1% yield). ¹H NMR (500 MHz, DMSO-d₆) δ 11.44 (brs, 1H), 8.58 (s, 1H), 8.54-8.47 (m, 1H), 7.18 (br d, J=8.5 Hz, 1H), 7.13(s, 1H), 7.09 (t, J=7.0 Hz, 1H), 4.06 (s, 3H), 3.30 (br s, 1H), 3.17 (s,2H), 3.07 (s, 3H), 3.01-2.88 (m, 3H), 2.88-2.78 (m, 3H), 2.20 (br t,J=10.5 Hz, 3H), 1.83-1.75 (m, 3H), 1.73 (br s, 4H), 1.36 (br d, J=6.4Hz, 6H). LCMS MH⁺: 493. HPLC Ret. Time 1.30 min. Method QC-ACN-AA-XB.

The following examples were prepared in a manner similar to thatdescribed in Example 991.

TABLE 26 Ex. LCMS R_(t) No. Structure MH⁺ (min) HPLC Method 992

464.5 1.5 QC-ACN-AA-XB 993

522 1.7 QC-ACN-AA-XB

Example 9944-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboximidamide

6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine(15.77 mg, 0.042 mmol) was stirred with 1H-pyrazole-1-carboximidamide(5.81 mg, 0.053 mmol) and DIPEA (0.037 mL, 0.211 mmol) in DMF (0.422 mL)at 75° C. for 8 h. DMF (1 mL) was added to the reaction mixture and thereaction mixture was purified via preparative LC/MS with the followingconditions: Column: XBridge C18, 19×200 mm, 5-μm particles; Mobile PhaseA: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B:95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-55% Bover 19 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min.Fractions containing the product were combined and dried via centrifugalevaporation to afford4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carboximidamide(8.4 mg, 0.019 mmol, 45.0% yield). LCMS MH⁺: 416.2 HPLC Ret. Time 1.23min. Method QC-ACN-AA-XB. ¹H NMR (500 MHz, DMSO-d₆) δ 9.29 (s, 1H), 8.39(s, 1H), 7.99 (s, 1H), 7.33-7.33 (m, 1H), 7.31 (d, J=7.9 Hz, 1H), 7.15(s, 1H), 7.11 (br d, J=8.1 Hz, 1H), 2.99-2.88 (m, 3H), 2.79 (s, 2H),2.77-2.70 (m, 1H), 2.16-2.06 (m, 1H), 1.74-1.64 (m, 2H), 1.51 (s, 4H),1.50-1.40 (m, 2H), 1.08-0.98 (m, 6H).

Biological Assays

The pharmacological properties of the compounds of this invention may beconfirmed by a number of biological assays. The exemplified biologicalassays, which follow, have been carried out with compounds of theinvention.

TLR7/8/9 Inhibition Reporter Assays

HEK-Blue™-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9receptors were used for screening inhibitors of these receptors using aninducible SEAP (secreted embryonic alkaline phosphatase) reporter geneunder the control of the IFN-β minimal promoter fused to five NF-κB andAP-1-binding sites. Briefly, cells are seeded into Greiner 384 wellplates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 forTLR9) and then treated with test compounds in DMSO to yield a final doseresponse concentration range of 0.05 nM-50 μM. After a 30 minutecompound pre-treatment at room temperature, the cells are thenstimulated with a TLR7 ligand (gardiquimod at a final concentration of7.5 μM), TLR8 ligand (R848 at a final concentration of 15.9 μM) or TLR9ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB andAP-1 which induce the production of SEAP. After a 22 hour incubation at37° C., 5% CO₂, SEAP levels are determined with the addition ofHEK-Blue™ Detection reagent (Invivogen), a cell culture medium thatallows for detection of SEAP, according to manufacturer'sspecifications. The percent inhibition is determined as the % reductionin the HEK-Blue signal present in wells treated with agonist plus DMSOalone compared to wells treated with a known inhibitor.

TABLE 27 TLR7/8/9 Reporter Assay Data TLR7 TLR8 TLR9 Ex. IC₅₀ IC₅₀ IC₅₀No. (nM) (nM) (nM) 1 34.5 69 3177 2 3.7 5.1 9015 3 3.9 2.2 1912 4 0.30.7 1589 5 0.5 2.7 818 6 1.1 9.8 1193 7 0.7 4.7 6636 8 0.3 2.2 1172 9 —0.5 21167 10 0.5 1.7 479 11 0.3 2.4 5385 12 0.8 1.9 3063 13 1 2.5 477814 2.4 1.5 23273 15 1.4 1.4 5113 16 1 1.6 6321 17 1.9 0.5 2501 18 1.51.5 15008 19 1 0.9 4802 20 2.1 0.8 2694 21 0.7 7.6 — 22 — 2 1845 23 0.43.3 4811 24 0.4 0.8 2865 25 0.3 3 2425 26 0.9 6.8 11110 27 0.8 3.4 176728 0.9 3.7 3052 29 0.3 1.8 1159 30 0.8 1.2 1534 31 0.7 1.5 1998 32 0.51.8 2399 33 8.5 22.9 13118 34 18.6 136.1 50000 35 0.5 2.2 1426 36 0.63.9 3545 37 0.6 1.2 1907 38 1.8 3.3 29477 39 1.1 0.8 4245 40 0.7 0.52462 41 0.5 1.2 4334 42 1.6 0.7 3114 43 2.3 1.1 7816 44 0.8 7 11301 450.3 1.1 1757 46 0.5 5.5 3032 47 4.8 45.5 10643 48 2.1 83.7 9585 49 14.256.8 50000 50 0.8 6.2 3409 51 12.2 61.4 4680 52 1.8 50.4 44293 53 32.2210.6 50000 54 0.6 34.6 30085 55 3.1 86.3 6521 56 1.5 23.9 1602 57 4.77.4 3749 58 2.7 41.6 2939 59 4.3 65.9 3116 60 1.2 42.5 40436 61 1.6 78.842221 62 0.7 4.5 644 63 1.8 46.5 37047 64 1.4 61.6 — 65 10.1 175.6 1113866 0.7 3.7 2659 67 1.1 9.2 5849 68 1.4 29 42823 69 2.1 13.1 3833 70 82.4558.7 50000 71 1.1 10.7 2476 72 0.4 7.5 1383 73 0.9 6 1270 74 2.9 3.36631 75 1 3.9 7158 76 0.8 3.7 2587 77 0.6 2.5 1579 78 0.7 5.8 7303 791.4 3.5 6255 80 1 6.1 2209 81 0.8 7 29110 82 0.5 4.7 1654 83 0.9 4 195884 0.6 3.8 974 85 0.6 2.9 481 86 1 2.5 2326 87 1 5.7 36053 88 1.2 3.72005 89 0.9 6.1 1594 90 0.2 3.4 1388 91 1 1.3 2784 92 1.2 3.3 6613 93 15.6 2645 94 0.3 5.7 3200 95 0.4 18.9 1964 96 0.6 19.7 1281 97 3.5 5.21549 98 0.8 2.0 1756 99 29.3 33.5 4652 100 8.6 169.4 1721 101 10.9 16.811330 102 116.8 3125.0 13829 103 5.3 174.1 2192 104 7.0 10.0 1722 1050.8 27.1 813 106 126.2 3125.0 12485 107 2.1 5.3 2330 108 79.7 29.0 4236109 153.0 699.9 427 110 1.5 4.5 1516 111 1.0 1129 112 1.1 16.6 1974 1180.8 3.3 2382 119 0.2 0.6 2487 120 3.4 47.5 2015 121 20.1 15.5 519 1229.6 89.5 663 123 28.9 32.0 2091 124 4.6 33.7 5036 125 5.0 67.2 1695 12618.7 312.9 605 127 81.5 21.6 1339 128 0.4 12.1 2648 131 109.2 16.6 1605132 2.6 8.2 844 133 1.1 9.5 1436 134 1.0 10.3 1076 135 3.2 30.0 291 13642.1 189.3 2708 138 0.3 19.6 760 140 0.7 7.2 2512 141 0.9 13.2 1331 14258.4 1543.0 343 143 5.7 — 424 144 2.0 7.8 779 145 9.9 92.0 2127 146 27.1178.6 1487 147 92.1 730.8 19901 148 12.8 4.2 602 149 47.3 709.4 214 150142.1 338.2 692 151 0.3 5.0 1567 152 0.8 3.7 1148 153 6.4 144.5 3429 15410.4 35.4 1064 155 599.7 191.0 862 156 2.8 17.2 2267 157 0.8 3.0 1149158 0.7 2.9 1927 159 7.0 63.2 8794 160 0.7 5.4 4991 161 1.8 13.4 1402162 3.2 45.3 1711 163 86.4 73.6 4947 164 9.0 15.0 3664 165 2.1 7.4 1816166 2.7 17.8 3220 167 0.8 4.3 2471 168 0.4 1.9 3414 169 1.2 12.5 7752170 1.2 4.4 8087 171 1.3 3.7 11528 172 0.4 4.1 5243 173 2.3 14.6 2860174 0.5 2.1 3681 175 0.8 5.8 23314 176 0.5 1.9 1708 177 1.0 2.3 10674178 0.8 3.5 1802 179 1.3 3.9 2038 180 33.6 5.9 12825 181 1.9 2.6 1770182 12.6 0.8 4939 183 8.4 2.0 5208 184 3.3 2.0 5470 185 7.7 3.3 6266 1865.2 8.3 14248 187 12.0 3.0 14559 188 6.5 1.9 17971 189 6.5 1.7 2760 1902.3 11.0 12310 191 14.8 6.8 6359 192 8.7 3.3 9593 193 5.7 44.0 4975 1945.0 22.3 15692 195 1.6 35.9 3957 196 1.3 25.1 8048 197 2.9 79.6 15694198 2.7 9.8 4107 199 1.8 12.8 8321 200 8.0 17.1 34036 201 1.8 9.6 1952202 1.4 16.7 15339 203 2.3 6.9 6028 204 0.7 0.7 2020 205 0.6 0.9 2764206 0.9 1.5 5737 207 10.8 8.8 4618 208 14.2 4.0 5041 209 3.9 5.9 8219210 3.4 6.2 4283 211 14.8 211.6 14365 212 10.6 347.6 2855 213 5.0 103.37241 214 5.2 111.2 16506 215 15.5 142.8 7579 216 3.2 243.5 19247 217 8.2238.7 8148 218 5.2 103.9 11257 219 34.0 18.3 10959 220 0.7 3.2 672 2210.4 1.3 5315 222 1.0 6.2 18169 223 0.8 12.0 1074 224 1.5 9.5 6973 2259.9 249.7 12206 226 8.9 8.9 18002 227 11.6 20.8 5074 228 78.3 962.038220 229 2.0 43.5 1047 230 68.1 51.4 7285 231 2.4 6.0 6641 232 2.3 7.01099 233 1.0 1.5 15605 234 0.6 6.2 7219 235 1.7 10.4 3087 236 19.6 9.11180 237 10.8 588.3 5935 238 8.9 347.5 2625 239 22.5 96.7 — 240 6.6 22.96003 241 18.9 4.9 2988 242 2.9 5.6 3600 243 2.8 33.5 44062 244 1.0 10.06270 245 1.2 10.5 2648 246 0.2 2.3 2259 247 7.4 48.5 4394 248 4.2 65.74582 249 11.5 20.1 1823 250 0.7 8.6 3422 251 0.5 7.8 6316 252 0.5 2.02551 253 0.2 13.6 1001 254 0.6 6.1 16008 255 95.0 1125.6 3771 256 178.61881.8 2121 257 1703.8 435.7 995 258 1235.5 404.7 5885 259 12.2 137.11355 260 0.4 13.9 2603 261 2.1 28.3 8114 262 0.6 5.3 1895 263 1.1 2.85301 264 0.5 2.3 3949 265 0.7 9.3 7028 266 560.4 448.9 7984 267 102.930.8 7300 268 2.8 15.7 1894 269 4.2 37.1 12314 270 5.2 4.6 1573 271 0.612.8 1346 272 0.6 11.7 2416 273 2.1 4.7 973 274 1.1 19.0 3731 275 3.125.5 10188 276 5.4 52.0 1824 277 10.4 61.2 2442 278 100.6 70.6 2134 27961.7 58.7 3164 280 0.6 12.4 4300 281 0.7 15.0 6153 282 1.7 5.9 10082 2834.9 6.3 2430 284 3.3 8.0 1900 285 1.5 15.1 6012 286 0.5 0.8 3147 287 1.00.5 3056 288 0.6 1.4 14105 289 1.0 25.9 6126 290 1.8 35.6 6254 291 8.22.1 1568 292 18.3 1.4 1303 293 0.5 15.8 5709 294 0.8 21.1 19539 295 1.945.6 2449 296 3.1 47.4 10442 297 5.0 26.3 2153 298 10.8 45.7 625 29926.3 139.7 3432 300 29.0 113.1 2658 301 54.5 252.5 6442 302 4.3 6.1 2971303 1.6 7.0 17114 304 0.9 3.3 4541 305 2.7 1.8 7034 306 1.2 2.7 16966307 48.2 103.0 5320 308 40.0 2.1 1533 309 43.1 2.0 709 310 181.4 307.2112 311 90.5 352.3 155 312 5.7 55.6 4305 313 5.4 80.6 3132 314 11.9 18.31640 315 268.6 557.9 1931 316 318.9 491.7 3692 317 19.8 71.8 8575 3186.8 25.5 2227 319 0.2 7.9 10520 320 0.3 14.2 3024 321 0.7 4.6 6178 3222.0 7.7 2086 323 2.6 35.3 5189 324 1.6 2.9 1001 325 1.4 12.4 1114 3261.2 6.7 2187 327 0.9 4.1 1453 328 4.3 4.3 1901 329 3.2 18.5 1051 330 1.014.4 1121 331 2.5 6.4 5294 332 3.6 4.1 3165 333 3.3 5.3 3183 334 2.9 1.92092 335 1.1 6.3 1501 336 4.9 4.7 2835 337 2.0 5.2 2106 338 1.6 5.8 8874339 4.1 5.6 14877 340 1.5 6.5 5866 341 1.9 4.2 2860 342 3.7 3.0 1785 3433.6 19.0 330 344 1.5 13.4 5474 345 5.1 37.6 1412 346 4.2 66.6 4614 3471511.5 2255.2 8618 348 5.5 — 1145 349 1.5 3.9 1787 350 5.6 12.5 4809 35139.9 18.4 5322 352 29.5 56.5 11409 353 38.5 44.2 24690 354 18.2 12.52258 355 8.3 107.0 6231 358 13.6 29.7 6035 359 6.8 8.9 1819 360 3.5 22.33619 361 14.4 9.9 9225 362 325.0 149.2 15799 363 19.4 10.1 822 364 9.27.0 1523 365 5.6 10.6 3587 366 29.0 8.7 1917 367 16.3 3.8 4404 368 57.019.1 2067 369 19.2 4.7 1839 370 23.4 15.8 2260 371 17.0 6.1 1927 37237.1 21.1 3472 373 21.4 6.5 2329 374 32.2 17.2 10078 375 11.6 10.3 2104376 9.5 5.2 1996 377 9.0 3.0 — 378 11.1 8.6 5732 379 2.7 1.2 990 380 6.712.1 1195 381 7.8 2.4 764 382 19.9 3.8 1894 383 79.8 59.6 18177 384 5.97.0 2266 385 7.8 62.9 31598 386 0.9 9.3 5157 387 1.4 6.1 3362 388 1.67.1 6145 389 2.8 2.1 7128 390 33.2 151.4 50000 391 0.2 0.9 1904 392 1.76.0 50000 393 2.7 1.5 1484 394 1.2 2.7 1379 395 2.3 10.4 44660 396 2.68.9 5113 397 0.6 2.9 2183 398 6.3 41.9 12558 399 1.1 3.8 857 400 2.513.5 2003 401 5.9 98.5 21445 402 2.5 8.6 6271 403 5.5 12.9 1662 404 1.37.2 50000 405 2.1 1.9 2379 406 0.6 1.8 747 407 1.5 1.9 2290 408 2.0 4.99828 409 0.5 1.1 658 410 1.5 1.0 1150 411 1.7 7.8 45491 412 0.5 1.8 2865413 1.2 33.5 632 414 1.4 4.9 3627 415 2.7 4.9 2503 416 5.4 16.4 22305417 10.1 46.9 26022 418 5.4 11.8 7590 419 1.1 2.6 279 420 1.0 1.5 725421 2.2 5.2 3405 422 0.6 3.3 7855 423 0.9 3.3 8387 424 1.0 4.3 3152 4253.7 5.1 1149 426 9.8 877.3 50000 427 1.6 5.9 3650 428 1.3 9.1 9034 4291.6 5.3 2074 430 0.7 3.1 3572 431 2.6 9.0 5462 432 0.1 1.8 1552 433 6.36.6 32563 434 1.4 3.7 5273 435 7.7 11.8 24316 436 3.0 3.3 6254 437 0.80.7 1186 438 2.7 5.7 2205 439 7.7 17.3 23290 440 3.4 5.7 24466 441 8.510.0 41305 442 9.1 3.9 2823 443 19.7 3.4 5143 444 42.1 5.4 16934 44513.6 1.6 3324 446 41.5 6.3 43852 447 55.8 10.8 50000 448 7.8 0.5 2338449 13.6 4.4 7125 450 15.8 2.0 11508 451 14.5 2.5 5148 452 11.0 2.8 996453 20.9 3.4 18886 454 38.9 3.1 10042 455 7.3 1.4 2198 456 98.6 27.615101 457 16.4 1.6 6631 458 7.8 8.1 30283 459 14.4 6.4 13406 460 7.3 6.050000 461 4.3 1.1 — 462 3.0 2.2 — 463 41.4 3.6 6221 464 3.1 3.8 13473465 18.5 1.8 4038 466 21.7 3.1 8713 467 14.1 2.2 4589 468 3.7 11.4 2776469 4.5 37.1 10275 470 8.2 10.0 3881 471 8.5 14.7 5311 472 5.3 2.6 2659473 6.0 16.9 25227 474 — 13.6 2095 475 0.5 1.8 4172 476 0.4 0.8 1355 4776.1 49.1 50000 478 1.7 0.7 2435 479 2.9 3.7 3906 480 0.6 1.0 4213 4810.7 0.8 2203 482 2.1 11.8 4192 483 5.2 1.6 28163 484 6.5 6.3 50000 4850.8 1.4 3415 486 1.3 1.0 3158 487 7.1 11.2 17398 488 3.6 2.1 4172 489 —2.7 4570 490 10.3 156.9 9234 491 11.5 49.9 2983 492 5.6 173.4 16217 4937.1 76.4 3973 494 5.5 82.8 6106 495 14.4 186.5 10106 496 6.4 104.3 8003497 2.2 97.2 4370 498 6.5 154.2 9516 499 55.0 31.2 50000 500 0.7 6.81348 501 1.5 11.4 8063 502 11.9 47.9 3449 503 — 143.5 50000 504 12.4 7.147457 505 4.4 2.5 3098 506 4.0 28.4 6661 507 645.6 3125.0 25265 508 51.014.0 48633 509 59.8 5.9 2801 510 1.4 4.6 15300 511 5.2 6.2 5624 512 2.81.2 2568 513 2.6 2.6 4138 514 3.1 1.9 3749 515 1.5 1.2 1675 516 3.3 1.43510 517 5.7 1.5 6413 518 1.9 2.5 11591 519 3.0 2.4 3723 520 2.8 3.26885 521 2.6 3.9 4828 522 4.5 6.2 25614 523 2.5 3.6 3660 524 1.4 4.36234 525 8.3 4.3 13427 526 4.4 1.8 2474 527 4.4 1.5 569 528 30.8 16.59591 529 33.7 17.0 10201 530 10.5 7.0 653 532 33.3 435.3 55 533 8.0281.1 1227 534 27.4 677.0 7557 535 29.9 209.0 1443 536 8.4 15.9 3538 5372.2 3.3 6503 538 0.5 12.5 1459 539 1.2 15.1 3234 540 0.4 1.5 1836 5410.3 1.8 1637 542 2.3 56.7 50000 543 1.7 11.0 1632 544 1.8 6.5 5008 5451.5 4.9 1301 546 71.6 85.3 7699 547 42.4 135.0 6042 548 5.5 30.0 4303549 1.5 20.7 — 550 1.3 7.7 6413 551 0.8 6.1 2317 552 0.6 3.5 995 553 5.329.0 3486 554 1.8 10.9 6093 555 0.3 2.1 2160 556 0.4 5.5 3924 557 0.46.5 2730 558 3125.0 3125.0 16753 559 634.2 288.6 483 560 1308.6 149.41897 561 1.5 5.8 1327 562 2.2 6.2 6348 563 0.8 2.6 1133 564 0.4 1.8 1234565 0.4 1.2 549 566 0.3 1.2 1469 567 0.4 3.0 2235 568 0.7 1.8 1451 5690.4 1.3 1565 570 0.4 0.7 535 571 5.1 1.9 1238 572 20.3 30.5 24538 5732.6 3.6 1571 574 — 20.5 6570 575 1.1 8.0 1859 576 0.9 6.5 1914 577 2.09.7 2237 578 5.4 23.2 7859 579 2.1 18.7 1799 580 4.1 84.8 5087 581 31.51.9 2472 582 0.6 3.6 2556 583 1.0 12.2 13615 584 2.1 12.1 3296 585 6.495.3 25590 586 34.6 84.5 2111 587 4.4 7.9 7380 588 2.4 10.6 50000 5892.6 0.7 4122 590 172.6 132.0 6275 591 180.4 2.0 5677 592 384.6 353.6 81593 0.7 16.1 1785 594 10.8 85.1 3928 595 4.1 15.9 14361 596 4.3 12.216277 597 8.8 44.3 10928 598 5.2 49.6 6302 599 2.9 10.9 1738 600 6.514.1 2652 601 28.7 147.9 50000 602 2.8 41.8 — 603 2.1 50.0 42404 604 4.5132.1 37270 605 0.8 25.8 40711 606 0.7 36.1 43596 607 0.9 42.6 44356 6081.8 55.6 50000 609 69.6 243.3 50000 610 1.7 13.7 5711 611 3.2 6.1 3382612 5.6 174.9 2353 613 48.8 3125.0 50000 614 56.3 3125.0 47110 615 12.8470.8 1595 616 12.5 607.4 901 617 32.7 3125.0 50000 618 9.1 634.9 2547619 19.3 310.2 50000 620 0.7 1.3 58 621 16.3 258.0 6809 622 1.3 21.61590 623 2.7 9.1 1106 624 1.6 12.1 1490 625 0.9 11.2 554 626 0.5 6.73181 627 0.4 11.3 5872 628 — 231.9 50000 629 0.7 7.4 3171 630 1.1 8.71988 631 3.5 66.9 45473 632 2.4 56.5 37917 633 568.1 3125.0 50000 6348.7 31.5 35483 635 3.1 17.0 1515 636 2.4 16.3 2448 637 34.0 1077.5 42907638 5.8 152.6 3221 639 5.0 140.1 3028 640 1838.5 3125.0 3723 641 0.314.9 1067 642 0.2 14.0 2517 643 0.6 197.5 22162 644 4.8 34.7 5784 6452.8 240.1 50000 646 5.7 538.0 50000 647 1.3 202.1 50000 648 14.7 1700.850000 649 1.6 10.1 7355 650 16.3 931.3 50000 651 3.2 260.9 12737 652 1.5157.2 36400 653 24.0 3125.0 50000 654 7.9 603.3 50000 655 1.4 115.5 9585656 131.7 2533.8 707 657 416.4 3125.0 50000 658 385.2 3125.0 50000 659809.7 3125.0 3750 660 1717.8 268.1 1001 661 868.3 85.9 544 662 1.0 14.01349 663 1.6 43.5 50000 664 2.2 56.9 5998 665 4.1 77.9 11847 666 5.855.4 12108 667 3.0 8.6 4501 668 1.2 36.9 34156 669 311.0 3125.0 50000670 8.3 59.6 50000 671 2.1 30.3 18365 672 1.0 8.4 2519 673 1.9 29.242411 674 1.2 14.4 663 675 0.8 14.5 3586 676 7.8 64.6 1693 677 1.9 43.833978 678 3.0 39.3 42260 679 0.4 5.2 1181 680 2.7 25.9 956 681 5.5 47.71195 682 1261.1 8.2 778 683 — 1.7 124 684 57.2 338.4 1468 685 12.4 590.150000 686 0.6 13.9 2172 687 1.0 15.1 1738 688 — 18.6 4136 689 0.5 3.32779 690 9.4 4.9 901 691 50.6 6.2 408 692 10.8 81.2 2415 693 6.6 46.7893 694 5.8 70.3 1288 695 6.2 23.5 1082 696 0.2 13.4 1547 697 0.2 9.31093 698 2.6 41.4 1434 699 1.1 18.1 1215 700 1.8 25.6 1844 701 2.4 8.02048 702 2.9 9.9 658 703 2.9 10.7 4601 704 1.1 5.6 2013 705 6.6 217.732501 706 2.3 30.3 473 707 5.2 156.8 27366 708 6.0 55.2 2110 709 6.3357.5 8846 710 16.2 290.8 16893 711 3.6 35.1 989 712 1.6 49.1 3058 71324.4 177.5 6626 714 0.8 3.7 2537 715 0.2 3.6 3257 716 0.6 117.2 43816717 5.5 46.3 46627 718 3.4 36.7 44471 719 0.5 3.1 616 720 5.2 35.4 5037721 3.9 9.9 190 722 3.3 17.5 2973 723 2.9 21.0 7713 724 1.4 4.4 782 72511.6 55.4 50000 726 10.7 35.8 50000 727 1.7 9.8 4497 728 3.0 15.4 3903729 2.2 5.4 462 730 27.4 152.8 13740 731 1.7 8.6 3025 732 2.3 7.6 3127733 10.1 78.2 23792 734 1.4 6.6 2862 735 1.2 7.7 1963 736 1.2 5.9 812737 1.1 5.9 4342 738 0.4 5.5 4312 739 2.0 11.2 15195 740 1.0 4.7 2044741 12.2 93.6 50000 742 1.0 9.2 5878 743 0.9 5.1 2418 744 3.7 13.4 1387745 0.7 5.1 1440 746 4.5 12.9 4678 747 3.5 20.0 6211 748 1.8 14.3 3623749 0.8 3.5 1354 750 1.3 5.4 1632 751 2.7 11.6 2560 752 33.7 144.7 50000753 0.9 4.3 1923 754 1.4 9.5 3789 755 2.1 7.8 1019 756 0.9 2.7 1275 7571.8 5.9 782 758 1.0 8.1 2893 759 0.7 12.5 3997 760 1.2 8.0 2950 761 8.971.5 50000 762 0.9 8.1 5102 763 2.5 8.1 4756 764 1.4 10.9 4042 765 0.93.4 1182 766 1.3 11.4 4842 767 0.2 2.7 2496 768 2.3 12.5 6751 769 1.07.3 1769 770 0.7 7.4 1794 771 1.5 12.3 2281 772 1.7 30.2 4855 773 1.011.9 3304 774 0.5 5.9 1009 775 0.7 5.6 1735 776 0.4 5.8 1398 777 0.422.6 4974 778 0.3 17.0 2934 779 1.1 64.8 7100 780 0.4 8.0 6227 781 — 4.3368 782 1.6 6.2 5308 783 0.5 4.1 3026 784 2.3 6.3 6602 785 1.0 5.8 — 7862.0 8.9 5342 787 0.8 4.1 3246 788 2.6 7.5 4575 789 4.2 15.5 4153 790 1.86.7 5742 791 1.7 9.7 5028 792 1.3 6.4 3377 793 1.5 5.9 4963 794 2.9 13.95588 795 2.2 8.6 3548 796 1.7 7.2 5141 797 1.4 5.4 4075 798 2.1 7.9 3146799 8.3 18.1 6791 800 8.5 37.4 16645 801 1.8 10.5 2874 802 3.3 5.8 5686803 7.6 10.0 41531 804 5.1 5.2 5283 805 2.4 6.3 2830 806 1.6 4.3 22288807 11.5 7.1 16216 808 8.5 5.8 5987 809 17.3 10.3 6047 810 6.6 4.3 3609811 1.1 13.8 4068 812 1.3 14.4 3769 813 7.8 14.5 5006 814 1.7 19.8 5168815 9.2 46.0 7886 816 4.8 38.1 20361 817 5.3 55.5 5416 818 4.7 18.0 3734819 6.3 39.7 8031 820 3.8 23.5 6111 821 8.2 61.0 22760 822 9.8 44.2 4011823 6.7 26.9 3040 824 16.3 76.4 16936 825 11.5 34.3 5468 826 13.4 30.36312 827 15.5 23.7 7064 828 16.3 73.1 12747 829 4.8 32.1 1999 830 6.737.8 9523 831 9.5 68.3 23615 832 11.3 61.7 50000 833 13.0 43.9 10940 83420.0 91.8 17529 835 9.9 33.3 3968 836 10.6 33.4 3228 837 10.4 35.7 5202838 622.3 2352.4 28501 839 6.0 21.0 5577 840 17.0 82.8 50000 841 16.9112.1 31037 842 58.2 342.0 50000 843 1.3 1.7 3654 844 6.0 9.0 23608 8451.4 1.1 9868 846 1.1 1.3 14078 847 1.6 1.1 4430 848 0.7 2.1 4492 849 0.91.4 5017 850 5.8 206.0 5624 851 1.0 14.3 — 852 3.5 34.6 10807 853 0.53.2 2064 854 0.4 4.9 13602 855 2.4 7.6 7042 856 2.0 16.5 8337 857 1.313.3 16943 858 0.8 2.4 3330 859 0.7 6.8 3367 860 1.7 24.5 35290 861 0.86.0 13098 862 0.3 2.9 1324 863 0.4 2.0 182 864 0.4 3.5 3008 865 0.2 3.44108 866 1.1 2.8 312 867 1.1 4.6 1371 868 0.5 5.6 2088 869 2.0 11.8 2042870 0.5 4.7 3106 871 0.7 6.9 2472 872 0.5 7.2 2838 873 0.8 8.6 3913 8741.7 10.9 766 875 0.4 6.5 2240 876 4.5 3.9 10992 877 5.3 1.9 16225 8781.8 2.0 5697 879 2.2 4.9 5146 880 2.0 1.3 6187 881 2.9 5.0 6005 882 4.731.3 37052 883 2.7 21.3 12076 884 12.1 71.7 50000 885 20.7 18.5 15041886 3.4 11.6 467 887 2.5 11.6 1836 888 1.0 4.8 1776 889 2.0 7.6 421 8904.9 24.0 4315 891 0.2 5.2 534 892 1.6 7.5 1379 893 1.3 5.0 1100 894 2.31.8 3303 895 1.1 3.3 1000 896 2.4 9.4 2732 897 1.2 2.2 2357 898 2.2 12.03608 899 3.8 21.2 2298 900 4.1 19.7 16642 901 2.5 8.7 1286 902 1.4 7.0707 903 1.6 6.4 724 904 1.1 4.9 1239 905 1.1 4.4 567 906 6.2 22.8 8854907 1.1 3.9 1053 908 3.8 17.8 2192 909 1.4 4.0 460 910 1.6 7.2 789 9111.0 5.6 1386 912 3.2 7.4 439 913 9.2 40.7 50000 914 0.9 4.2 1410 915 1.14.5 1361 916 1.6 5.5 1958 917 1.1 4.3 1539 918 1.9 11.2 3508 919 3.821.0 3197 920 3.9 15.2 1524 921 1.4 10.0 2943 922 3.0 12.4 3234 923 1.66.6 652 924 3.0 11.9 1986 925 1.0 7.9 2357 926 5.3 35.2 2859 927 0.9 6.03676 928 1.3 10.6 12118 929 0.8 3.1 1289 930 1.1 3.7 2277 931 1.0 3.91317 932 1.7 10.7 2686 933 1.5 3.9 1814 934 0.5 1.3 1715 935 0.4 3.9 875936 6.2 13.8 1601 937 1.4 3.1 1532 938 1.2 5.6 1698 939 2.1 7.0 1962 9400.7 2.6 1912 941 0.4 1.5 1520 942 2.5 14.7 7172 943 1.0 6.2 9610 944 2.017.2 7735 945 1.3 6.9 1954 946 9.5 38.9 30228 947 2.6 12.4 2448 948 24.3125.9 18223 949 18.6 128.9 18701 950 2.3 40.7 5688 951 0.9 10.1 3767 9523.4 35.9 27912 953 2.3 13.4 5808 954 1.2 4.0 2148 955 1.8 10.0 13172 9561.3 8.5 1629 957 1.1 21.0 50000 958 1.3 9.4 4557 959 69.8 186.9 24350960 2.5 12.3 5034 961 16.3 37.7 5021 962 6.0 12.7 2523 963 4.2 30.950000 964 3.7 7.7 1522 965 1.6 11.5 5622 966 14.8 31.8 3080 967 0.8 5.83780 968 12.1 24.4 3588 969 0.7 2.4 542 970 11.4 28.9 3387 971 20.9 22.32635 972 3.9 15.5 2311 973 32.8 134.2 50000 974 2.6 4.9 2241 975 2.9 5.22223 976 1.5 6.8 6155 977 1.0 1.6 604 978 2.0 3.4 3040 979 8.1 12.411509 980 1.9 3.6 868 981 16.9 249.7 7530 982 1.4 — 3106 983 69.2 258.96108 984 0.9 8.4 4750 985 2.4 59.6 4832 986 50.5 335.8 1256 987 196.7384.6 160 988 1835.0 3125.0 413 989 74.2 302.1 50000 990 1.9 12.1 2592991 0.5 1.8 5591 992 2.2 1.7 1461 993 2.0 5.4 6521 994 9.1 85.4 13067

Inhibition Data

In Vivo mouse TLR7 PD model:

Adult male C57BL/6 mice were used for the experiments. Mice (7 to 10 pergroup) were randomized into different treatment groups based on bodyweight. Mice from the respective treatment groups were administeredorally with vehicle or test compound. Thirty min after the oraladministration of vehicle or test compound, mice were challenged withintraperitoneal injection of gardiquimod for TLR7 PD model. Ninetyminutes after gardiquimod injection, mice were bled under isofluraneanaesthesia and plasma IL-6 and IFN-alpha levels were estimated by usingcommercially available ELISA kit (BD Biosciences, PBL Life Sciences). Atthe end of experiment, mean cytokine data was plotted and one way ANOVAwith Dunnett's test was performed to calculate the significance of testcompound treated group vs. vehicle control group. Percent inhibition ofcytokine induction was calculated for test compound treated group vsvehicle control group. Data from multiple studies with different testcompounds is shown in Table 28.

TABLE 28 Percent inhibition of IL-6 and IFN-alpha in mouse TLR7 PD modelEx. Dose No. (mg/kg) % inhibition of IL6 % inhibition of IFN-alpha 60.0000375 10 9 0.0001875 30 31 0.00075 56 55 0.003 64 66 0.015 86 96 150.000625 18 11 0.0025 49 27 0.01 65 62 0.04 84 88 0.16 91 99 18 0.000559 7 0.0022 22 10 0.0088 50 44 0.0352 60 66 0.1408 80 99 25 0.00096 22 20.00385 39 44 0.01540 62 62 0.06160 89 98 0.24640 95 100 26 0.000655 201 0.003276 40 33 0.01638 56 68 0.0819 91 99 0.4095 98 100

NZB/W Model of Systemic Lupus Erythematosus (SLE):

Female NZB/W mice of were screened and randomized based on the titers ofanti-dsDNA antibodies and urinary NGAL (Neutrophil Gelatinase AssociatedLipocalin). Mice were treated orally, once daily for 24 weeks withvehicle or test compound. The effect of test compound on diseaseseverity was assessed by measuring end points including proteinuria,urinary-NGAL, urinary TIMP 1, blood urea nitrogen (BUN), anti-dsDNA Abtiter, anti-smRNP Ab titer, and plasma levels of IL10 and IL12p40. Incase of BUN the absolute increase was measured by subtracting the BUNvalues estimated before the initiation of treatment, from BUN valuesestimated after the completion of treatment. At the end of experiment,all mice were euthanized by CO₂ asphyxiation and kidney samples weresubjected for histology. To calculate the significance of test compoundtreated group vs. vehicle control group, one way ANOVA with Dunnett'stest was performed. Percent reduction in disease severity was calculatedfor each parameter, for test compound treated group vs vehicle controlgroup. A cumulative disease score and the percent reduction incumulative disease score was calculated by considering the averageinhibition in proteinuria, urinary-NGAL, anti-dsDNA Ab titer and anti-smAb titer to reflect the impact on the overall severity of diseaseprogression. Data from multiple studies with different test compounds isshown in Table 30.

TABLE 30 Inhibition of Disease Development by TLR7/8 Inhibitors in NZB/WModel of Lupus % inhibition Anti- Anti- ds SmR DNA Cumu- Ex Dose Pro-Urinary Urinary NP Ab Ab IL-12p lative No (mg/kg) teinuria NGAL TIMP1BUN titer titer 40 IL-10 score 15 0.06 96 79 66 100 28 20 68 98 56 0.2596 84 73 100 48 34 78 93 66 0.75 98 86 72 100 51 45 81 93 70 2.5 97 9380 100 55 55 83 97 75 18 0.1 98 78 94 100 40 23 75 100 60 0.5 98 93 94100 52 33 88 98 69 1.5 99 93 95 100 61 43 87 100 74 5 98 93 92 100 66 5789 100 79 25 0.5 99 77 71 97 41 4 91 97 65 3 99 80 73 100 51 51 93 98 709 99 83 81 98 65 54 92 100 75 30 98 84 82 100 68 62 93 97 78

1-20. (canceled)
 21. A compound of Formula (I)

or a salt thereof, wherein: R₁ is H, Cl, —CN, C₁₋₄ alkyl, C₁₋₃fluoroalkyl, C₁₋₃ hydroxy-fluoroalkyl, —CR_(z)═CH₂, C₃₋₆ cycloalkyl,—CH₂(C₃₋₆ cycloalkyl), —C(O)O(C₁₋₃ alkyl), or tetrahydropyranyl; each R₂is independently halo, —CN, —OH, —NO₂, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl,C₁₋₂ cyanoalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl, —O(CH₂)₁₋₂OH,—(CH₂)₀₋₄O(C₁₋₄ alkyl), C₁₋₃ fluoroalkoxy, —(CH₂)₁₋₄O(C₁₋₃ alkyl),—O(CH₂)₁₋₂OC(O)(C₁₋₃ alkyl), —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃ alkyl),—C(O)NR_(y)R_(y), —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄hydroxyalkyl), —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl),—NR_(x)C(O)(C₁₋₃ alkyl), —NR_(x)(CH₂-cyclopropyl), C₃₋₆ cycloalkyl,morpholinyl, dioxothiomorpholinyl, methylpiperidinyl, methylpiperazinyl,amino-oxadiazolyl, imidazolyl, triazolyl, or —C(O)(thiazolyl); R₃ is-L₁-A; L₁ is —C(O)—; A is 2-oxa-6-azaspiro[3,3]heptanyl,4-oxaspiro[2.5]octanyl, 7-azaspiro[3.5]nonanyl,8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl,9-azabicyclo[3.3.1]nonanyl, adamantanyl, azepanyl, azetidinyl, C₃₋₆cycloalkyl, diazepanyl, dihydroinonyl, dihydropyrimidinonyl, dioxanyl,dioxidothiadiazinanyl, dioxidothiazolidinyl, dioxidothiomorpholinyl,dioxoisothiazolidinyl, dioxidothiazinanyl, dioxotetrahydrothiophenyl,dioxotetrahydrothiopyranyl, dioxothiomorpholinyl, furanyl, imidazolyl,imidazolidinonyl, indolyl, isoquinolinyl, isoxazolyl, morpholinyl,morpholinonyl, naphthalenyl, octahydrocyclopenta[b]pyranyl,octahydropyrrolo[3,4-b]pyridinyl, oxazolidinonyl, oxadiazolyl, oxazolyl,oxetanyl, phenyl, piperidinyl, piperidinonyl, piperazinyl,piperazinonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridazinonyl,pyridinonyl, pyridinyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl,pyrrolyl, quinolinyl, quinolizinonyl, tetrahydrofuranyl,tetrahydropyranyl, tetrahydrothiopyranyl, tetrazolyl, thiadiazolyl,thiazolyl, triazolonyl, or triazolyl, each substituted with -L₂-R_(a)and zero to 4 R_(b); L₂ is a bond or —CR_(x)R_(x)—; R_(a) is: (a) H, F,Cl, —CN, —OH, C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₅ hydroxyalkyl,—(CH₂)₀₋₄O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃S(C₁₋₃ alkyl),—(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₃NR_(y)R_(y),—(CR_(x)R_(x))₁₋₃C(O)NR_(y)R_(y), —O(C₁₋₃ fluoroalkyl),—S(O)₂NR_(x)R_(x), —O(CR_(x)R_(x))₁₋₃NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl),—NR_(x)R_(x), —NR_(x)(C₁₋₄ alkyl), —NR_(x)C(O)(C₁₋₄ alkyl),—(CR_(x)R_(x))₀₋₃C(O)OH, —C(O)(C₁₋₅ alkyl), —C(O)(C₁₋₃ fluoroalkyl),—C(O)O(C₁₋₄ alkyl), —C(O)NH(C₁₋₃ cyanoalkyl), —C(O)NR_(y)R_(y),—C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃ alkyl);(b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein each cycloalkylis substituted with zero to 2 substituents independently selected from—OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkyl, and —C(O)O(C₁₋₃alkyl); or (c) A₁, —CH₂A₁, —C(O)A₁, —NR_(x)A₁, or —C(O)NR_(x)A₁, whereinA₁ is furanyl, imidazolyl, indolyl, isoxazolyl, morpholinyl,octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl,piperazinonyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolyl,pyridinyl, pyrimidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolyl,tetrahydrofuranyl, tetrahydropyranyl, thiadiazolyl, thiazolyl,thiophenyl, or triazolyl, each substituted with zero to threesubstituents independently selected from —OH, C₁₋₃ alkyl, C₁₋₃hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃ alkyl), —NR_(x)R_(x),phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl), and—CH₂CH₂(pyrrolidinyl); each R_(b) is independently F, —OH, —CH₃, —CF₃,or —OCH₃; each R_(x) is independently H or —CH₃; each R_(y) isindependently H or C₁₋₆ alkyl; R_(z) is H, C₁₋₂ alkyl, or C₁₋₂fluoroalkyl; each R₄ is independently F, —OH, C₁₋₂ alkyl, or —OCH₃; ortwo R₄ attached to the same carbon atom form ═O; or wherein when m is atleast 2, two R₄, each attached to a different carbon atom adjacent tothe nitrogen atom in the piperidinyl ring, can form a —CH₂CH₂— bridge;each R₅ is independently F, Cl, —CN, C₁₋₂ alkyl, C₁₋₂ fluoroalkyl, or—OCH₃; m is zero, 1, 2, 3, or 4; n is zero, 1, or 2; and p is zero, 1,2, 3, or
 4. 22. The compound according to claim 1 or salt thereof,wherein: R₁ is H, Cl, —CN, C₁₋₄ alkyl, or C₁₋₂ fluoroalkyl; each R₂ isindependently F, Cl, —CN, —OH, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl, C₁₋₂cyanoalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl, —O(CH₂)₁₋₂OH, —O(C₁₋₄alkyl), C₁₋₂ fluoroalkoxy, —(CH₂)₁₋₄O(C₁₋₃ alkyl), —O(CH₂)₁₋₂OC(O)(C₁₋₃alkyl), —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃ alkyl), —C(O)NR_(y)R_(y),—NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄ hydroxyalkyl),—NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), —NR_(x)C(O)(C₁₋₃alkyl), —NR_(x)(CH₂-cyclopropyl), C36 cycloalkyl, morpholinyl,dioxothiomorpholinyl, methylpiperidinyl, methylpiperazinyl,amino-oxadiazolyl, imidazolyl, triazolyl, or —C(O)(thiazolyl); A isazetidinyl, C₃₋₆ cycloalkyl, dioxotetrahydrothiopyranyl,dioxidothiadiazinanyl, dioxidothiomorpholinyl, furanyl, imidazolyl,isoquinolinyl, morpholinyl, oxazolyl, 2-oxa-6-azaspiro[3.3]heptanyl,octahydropyrrolo[3,4-b]pyridinyl, oxetanyl, phenyl, piperazinonyl,piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridinyl,pyrrolidinonyl, pyrrolidinyl, pyrrolyl, quinolinyl, tetrahydrofuranyl,tetrahydropyranyl, tetrazolyl, thiadiazolyl, thiazolyl, or triazolyl,each substituted with -L₂-R_(a) and zero to 4 R_(b); R_(a) is: (a) H, F,—CN, —OH, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl,—(CH₂)₀₋₂O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl),—(CR_(x)R_(x))₁₋₃NH₂, —(CR_(x)R_(x))₁₋₃NR_(x)(C₁₋₄ alkyl), —O(C₁₋₂fluoroalkyl), —S(O)₂NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl), —NR_(x)R_(x),—NR_(x)(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₂C(O)OH, —C(O)OH, —C(O)(C₁₋₃alkyl), —C(O)O(C₁₋₄ alkyl), —C(O)NR_(x)(C₁₋₂ alkyl), —C(O)N(C₁₋₃alkyl)₂, —C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃alkyl); (b) C₃₋₆ cycloalkyl or —C(O)NH(C₃₋₆ cycloalkyl), wherein eachcycloalkyl is substituted with zero to 2 substituents independentlyselected from —OH, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C13 fluoroalkyl, and—C(O)O(C₁₋₃ alkyl); or (c) A₁, —CH₂A₁, —C(O)A₁, or —C(O)NHA₁, wherein A₁is furanyl, imidazolyl, indolyl, isoxazolyl,octahydropyrrolo[3,4-c]pyrrolyl, oxazolyl, oxetanyl, phenyl,piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridinyl, pyrimidinyl,pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl,thiadiazolyl, thiazolyl, thiophenyl, or triazolyl, each substituted withzero to three substituents independently selected from —OH, C₁₋₃ alkyl,C₁₋₃ hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃ alkyl), —NR_(x)R_(x),phenyl, trifluoromethylphenyl, —CH₂(bromophenyl), and—CH₂CH₂(pyrrolidinyl); each R₄ is independently F, —OH, C₁₋₂ alkyl, or—OCH₃; or two R₄ attached to the same carbon atom form ═O; R₅ is F, Cl,—CN, —CH₃, —CF₃, or —OCH₃; each R_(b) is independently —OH, —CH₃, or—CF₃; each R_(x) is independently H or —CH₃; each R_(y) is independentlyH or C₁₋₅ alkyl; m is zero, 1, or 2; n is zero or 1; and p is zero, 1,or
 2. 23. The compound according to claim 1 or salt thereof, wherein: R₁is —CH₂CH₃, —CH(CH₃)₂, or —CH₂CHF₂; each R₂ is independently F, Cl, —CN,—CH₃, —CH₂CH₃, —CH(CH₃)₂, —CF₃, —CH₂CN, —CH₂OH, —CH₂CH₂OH, —CH(CH₃)OH,—C(CH₃)₂OH, —OCH₂CH₂OH, —OCH₃, —OCH₂CH₃, —OCH₂CH(CH₃)₂, —OCHF₂,—CH₂OCH₃, —CH₂OCH₂CH₃, —OCH₂CH₂OC(O)CH₃, —NH₂, —NH(CH₂CH₃), —NH(CH₂CF₃),—NH(CH₂C(CH₃)₂OH), —NHCH₂(phenyl), —NHS(O)₂(cyclopropyl), cyclopropyl,morpholinyl, dioxothiomorpholinyl, or methylpiperazinyl; A isazetidinyl, C₃₋₆ cycloalkyl, furanyl, imidazolyl, morpholinyl, oxazolyl,octahydropyrrolo[3,4-b]pyridinyl, oxetanyl, phenyl, piperazinonyl,piperazinyl, piperidinyl, pyrazinyl, pyrazolyl, pyridinyl,pyrrolidinonyl, pyrrolidinyl, pyrrolyl, quinolinyl, tetrahydrofuranyl,tetrahydropyranyl, tetrazolyl, thiadiazolyl, thiazolyl, or triazolyl,each substituted with -L₂-R_(a) and zero to 4 R_(b); L₂ is a bond; R_(a)is: (a) H, F, —CN, —OH, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl,—(CH₂)₀₋₁O(C₁₋₃ alkyl), —(CR_(x)R_(x))₁₋₃NHC(O)O(C₁₋₄ alkyl),—(CR_(x)R_(x))₁₋₃NH₂, —(CR_(x)R_(x))₁₋₃NR_(x)(C₁₋₄ alkyl), —O(C₁₋₂fluoroalkyl), —S(O)₂NR_(x)R_(x), —NHS(O)₂(C₁₋₃ alkyl), —NR_(x)R_(x),—NR_(x)(C₁₋₄ alkyl), —(CR_(x)R_(x))₁₋₂C(O)OH, —C(O)OH, —C(O)(C₁₋₃alkyl), —C(O)O(C₁₋₄ alkyl), —C(O)NR_(x)(C₁₋₂ alkyl), —C(O)N(C₁₋₃alkyl)₂, —C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or —C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃alkyl); (b) C₃₋₆ cycloalkyl, wherein each cycloalkyl is substituted withzero to 2 substituents independently selected from —OH, C₁₋₃ alkyl, C₁₋₃hydroxyalkyl, C₁₋₃ fluoroalkyl, and —C(O)O(C₁₋₃ alkyl); or (c) A₁ or—CH₂A₁, wherein A₁ is furanyl, imidazolyl, indolyl, isoxazolyl,oxazolyl, oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazinyl,pyrazolyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl,tetrahydrofuranyl, tetrahydropyranyl, thiadiazolyl, thiazolyl,thiophenyl, or triazolyl, each substituted with zero to threesubstituents independently selected from —OH, C₁₋₃ alkyl, C₁₋₃hydroxyalkyl, —C(O)(C₁₋₂ alkyl), —C(O)O(C₁₋₃ alkyl), —NR_(x)R_(x),phenyl, trifluoromethyl-phenyl, —CH₂(bromophenyl), and—CH₂CH₂(pyrrolidinyl); R₅ is F, Cl, —CN, —CH₃, —CF₃, or —OCH₃; eachR_(b) is independently —OH, —CH₃, or —CF₃; m is zero or 1; n is zero;and p is zero, 1 or
 2. 24. The compound according to claim 1 or saltthereof, wherein: R₁ is —CH₂CH₃, —CH(CH₃)₂, or —CH₂CHF₂; each R₂ isindependently selected from F, Cl, —CN, —CH₃, or —CF₃; A is azetidinyl,C₃₋₄ cycloalkyl, morpholinyl, octahydropyrrolo[3,4-b]pyridinyl,oxetanyl, piperazinonyl, piperazinyl, piperidinyl, pyrrolidinonyl,pyrrolidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substitutedwith -L₂-R_(a) and zero to 4 R_(b); L₂ is a bond; R_(a) is: (a) H, F,—CN, —OH, C₁₋₃ alkyl, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl,—(CH₂)₀₋₁O(C₁₋₂ alkyl), —O(C₁₋₂ fluoroalkyl), —NR_(x)R_(x), —NR_(x)(C₁₋₄alkyl), —C(O)OH, —C(O)(C₁₋₃ alkyl), —C(O)O(C₁₋₄ alkyl), —C(O)NR_(x)(C₁₋₂alkyl), —C(O)N(C₁₋₃ alkyl)₂, —C(O)NR_(x)CH₂C(O)NR_(x)R_(x), or—C(O)NR_(x)CH₂CH₂NHC(O)(C₁₋₃ alkyl); or (b) A₁, wherein A₁ is furanyl,imidazolyl, indolyl, isoxazolyl, octahydropyrrolo[3,4-c]pyrrolyl,oxazolyl, oxetanyl, phenyl, piperazinyl, piperidinyl, pyrazinyl,pyrazolyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl,tetrahydrofuranyl, tetrahydropyranyl, thiadiazolyl, thiazolyl,thiophenyl, or triazolyl, each substituted with zero to threesubstituents independently selected from —OH, C₁₋₃ alkyl, C₁₋₃hydroxyalkyl, or —NR_(x)R_(x); m is zero or 1; n is zero; and p is zero,1 or
 2. 25. The compound according to claim 1 or salt thereof, wherein:R₁ is —CH(CH₃)₂; each R₂ is independently —CH₃, —CF₃, or —OCH₃; R₃ is-L₁-A; L₁ is —C(O)—; A is azetidinyl, cyclopropyl,octahydropyrrolo[3,4-b]pyridinyl, oxetanyl, piperazinonyl, piperazinyl,pyrrolidinonyl, pyrrolidinyl, or tetrahydrofuranyl; each substitutedwith -L₂-R_(a) and zero to 3 R_(b); L₂ is a bond; R_(a) is F, —OH, —CH₃,—CH₂CH₂CH₃, —CF₃, —CH₂CH₂OH, —OCH₃, —C(O)CH₃, —NH₂, —C(O)CH₃,—C(O)OC(CH₃)₃, pyrazinyl, or pyridinyl; each R_(b) is independently —OHor —CH₃; m is zero; n is zero; and p is zero, 1, or
 2. 26. The compoundaccording to claim 1 or a salt thereof, wherein said compound is:(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylcyclopropyl)methanone(55);(S)-azetidin-2-yl(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(56);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(3-methyloxetan-3-yl)methanone(64);4-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one (243);4-(4-(2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one(601);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-(pyrazin-2-yl)cyclopropyl)methanone(604);((2S,3R)-3-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(615);((2S,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(616);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (621);((2S,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(622);((2S,3R)-3-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(623);((2S,4S)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(624);((2R,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(625);(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)((2S,4R)-4-methoxypyrrolidin-2-yl)methanone (626);((2S,4R)-4-fluoropyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone(627);1-((2S,4R)-4-hydroxy-2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)pyrrolidin-1-yl)ethan-1-one(628); tert-butyl(2S,3R)-2-(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidine-1-carbonyl)-3-hydroxypyrrolidine-1-carboxylate(634);(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)((2S,3R)-3-hydroxypyrrolidin-2-yl)methanone (635);(4-(2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)((2S,4R)-4-hydroxypyrrolidin-2-yl)methanone (636);(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(tetrahydrofuran-2-yl)methanone(645);(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-(trifluoromethyl)cyclopropyl)methanone(653);(4-(3-isopropyl-2-(8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(oxetan-3-yl)methanone(654);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(tetrahydrofuran-2-yl)methanone (663);(S)-1-(2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)pyrrolidin-1-yl)ethan-1-one(670);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpyrrolidin-3-yl)methanone (672);((2S,4R)-4-hydroxypyrrolidin-2-yl)(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)methanone (674);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)((2S,4R)-4-methoxypyrrolidin-2-yl)methanone (675);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpyrrolidin-3-yl)methanone (676);4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one (677);4-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidine-1-carbonyl)-1-methylpyrrolidin-2-one (678);(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpyrrolidin-3-yl)methanone (679);(4-(3-isopropyl-2-(8-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)(1-methylpiperidin-4-yl)methanone(694);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-methylpiperazin-1-yl)methanone (957);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone (958);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)methanone((960);4-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-H-indol-5-yl)piperidine-1-carbonyl)-1-methylpiperazin-2-one (963);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-propylpiperazin-1-yl)methanone (965);(3-aminoazetidin-1-yl)(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)methanone(967);(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-(pyridin-4-yl)piperazin-1-yl)methanone (969); or(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-indol-5-yl)piperidin-1-yl)(4-isopropylpiperazin-1-yl)methanone (973).
 27. Thecompound according to claim 1 or a salt thereof, wherein said compoundis:


28. The compound according to claim 1 or a salt thereof, wherein saidcompound is:


29. The compound according to claim 1 or a salt thereof, wherein saidcompound is:


30. A pharmaceutical composition comprising a compound according toclaim 1 or a pharmaceutically-acceptable salt thereof; and apharmaceutically acceptable carrier.
 31. A pharmaceutical compositioncomprising a compound according to claim 27 or apharmaceutically-acceptable salt thereof; and a pharmaceuticallyacceptable carrier.
 32. A pharmaceutical composition comprising acompound according to claim 28 or a pharmaceutically-acceptable saltthereof; and a pharmaceutically acceptable carrier.
 33. A pharmaceuticalcomposition comprising a compound according to claim 29 or apharmaceutically-acceptable salt thereof; and a pharmaceuticallyacceptable carrier.
 34. A method of treating an autoimmune disease or achronic inflammatory disease, comprising administering to a mammalianpatent a compound according to claim 1 or a pharmaceutically acceptablesalt thereof, wherein said autoimmune disease or chronic inflammatorydisease is systemic lupus erythematosus.
 35. A method of treating anautoimmune disease or a chronic inflammatory disease, comprisingadministering to a mammalian patent a compound according to claim 27 ora pharmaceutically acceptable salt thereof, wherein said autoimmunedisease or chronic inflammatory disease is systemic lupus erythematosus.36. A method of treating an autoimmune disease or a chronic inflammatorydisease, comprising administering to a mammalian patent a compoundaccording to claim 28 or a pharmaceutically acceptable salt thereof,wherein said autoimmune disease or chronic inflammatory disease issystemic lupus erythematosus.
 37. A method of treating an autoimmunedisease or a chronic inflammatory disease, comprising administering to amammalian patent a compound according to claim 29 or a pharmaceuticallyacceptable salt thereof, wherein said autoimmune disease or chronicinflammatory disease is systemic lupus erythematosus.